Device and method for laser assisted deep sclerectomy

ABSTRACT

An ophthalmic laser ablation system is described with various optional features, some especially suitable for non-penetrating filtration on an eye. In one example, focusing of an ablation laser uses a movable lens coupled to a pair of converging light sources, which converge at the focal distance of the lens. In another example, laser ablation settings are selected for optimal ablation and minimal amount of thermal damage of a layer of percolating scleral tissue.

RELATED APPLICATION

This application claims the benefit under 35 USC 119(e) of U.S.Provisional Patent Application No. 61/193,865 filed on Dec. 31, 2008,and U.S. Provisional Patent Application No. 61/202,184 filed on Feb. 4,2009, the disclosures of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention, in some embodiments thereof, relates to methodsand systems for ameliorating raised inter ocular pressure, and moreparticularly but not exclusively to a laser ablation system fornon-penetrating sclerectomy.

BACKGROUND

Glaucoma is a group of diseases, frequently characterized by raisedintraocular pressure (IOP), which affects the optic nerve, and is thesecond leading cause of blindness in the world. Currently, most glaucomapatients are initially managed with medical therapy. However, somepatients still require surgical interventions to preserve their vision.When glaucoma continues to progress despite the use of medicationregimes and possibly laser treatments (ALT or SLT treatments), aglaucoma filtration procedure (trabeculectomy) may be recommended.Additional surgical techniques for reducing intraocular pressure (IOP)include laser trabeculoplasty, non-penetrating filtration surgery (i.e.deep sclerectomy, viscocanalostomy), shunts, and cyclo-destructiveprocedures.

Deep sclerectomy, a non-penetrating or minimally invasive filteringsurgery, is being proposed as a viable alternative to conventionaltrabeculectomy. In contrast to trabeculectomy, which is associated withsignificant morbidity, deep sclerectomy does not penetrate the eye, andhas been shown to minimize intraoperative and postoperativecomplications.

In a manual non-penetrating deep sclerectomy (NPDS) procedure performedwith manual surgical instruments, a deep scleral flap is first dissectedand then a second scleral layer is cut out, leaving an exposed thinlayer of trabecular meshwork and Descemet's membrane. Fluid percolationthrough the remaining tissue is the desired outcome of the procedure.Inadvertent perforation of the thin trabeculo-descemet membrane oralternatively an insufficiently deep second scleral flap, are relativelyfrequent complications, occurring in about 30% of the cases in the earlystages of the learning curve of this procedure. In the case ofperforation, the procedure may be converted to a conventionaltrabeculectomy; however, the high rates of perforation and a longlearning curve limit the use of deep sclerectomy as a common treatmentprocedure. While the risk of perforation is relatively high, if thetissue is not cut deep enough, the filtration may not be effective andthe intraocular pressure will not be reduced to the desired level. Sincethe scleral tissue needs to be dissected to more than 90% of its depth,leaving a residual intact layer of only several tens of microns, theprocedure is very demanding and requires significant skills andexpertise.

The following publications may be relevant to this application:

RE 37504 of U.S. Pat. No. 5,549,598 U.S. Pat. No. 3,828,788 U.S. Pat.No. 4,665,913 May 1987 L'Esperance, Jr. U.S. Pat. No. 4,907,586 March1990 Bille et al. U.S. Pat. No. 4,963,142 October 1990 Loertscher U.S.Pat. No. 5,098,426 March 1992 Sklar et al. U.S. Pat. No. 5,364,390November 1994 Taboada et al. U.S. Pat. No. 5,370,641 December 1994O'Donnell, Jr. U.S. Pat. No. 5,520,679 May 1996 Lin U.S. Pat. No.5,529,076 June 1996 Schachar U.S. Pat. No. 5,620,435 April 1997 Belkinet al. U.S. Pat. No. 5,634,920 June 1997 Hohla U.S. Pat. No. 5,733,276March 1998 Belkin U.S. Pat. No. 5,738,677 April 1998 Colvard et al. U.S.Pat. No. 5,782,822 July 1998 Telfair et al. U.S. Pat. No. 5,827,266October 1998 Harel et al. U.S. Pat. No. 6,010,497 January 2000 Tang etal. U.S. Pat. No. 6,059,772 May 2000 Hsia et al. U.S. Pat. No. 6,159,202December 2000 Sumiya et al. U.S. Pat. No. 6,220,247 April 2001 MaldonadoBas U.S. Pat. No. 6,241,721 June 2001 Cozean et al. U.S. Pat. No.6,258,082 July 2001 Lin U.S. Pat. No. 6,263,879 July 2001 Lin U.S. Pat.No. 6,540,391 April 2003 Lanzetta et al. U.S. Pat. No. 7,135,016 US2001/0029363 October 2001 Lin US 2002/0026179 February 2002 Toh US2005/0096639 EP 0 765 648 April 1997 EP 0 770 370 May 1997 EP 1 138 290October 2001 WO 01/50969 July 2001 WO 01/085044 WO 03/041623

-   Assia E. I. et al. Experimental studies on non-penetrating    filtration surgery using the CO2 laser. Graefes Arch Clin Exp    Ophthalmol. 2007 June; 245(6):847-54-   Barak, A. et al; “Anterior Capsulotomy Using CO2 Laser;” SPIE; vol.    3246; pp. 196-198; June 1998.-   Assia, E. I. et al.; “Non-Penetrating Glaucoma Surgery Using the    CO.sub.2 Laser: Experimental Studies in Human Cadaver Eyes;”    Proceedings of SPIE; vol. 4245; pp. 228-233; June 2001.-   Belkin, M. et al.; “Non-Penetrating Trabeculectomy Using the    CO.sub.2 Laser in Rabbits;” Abstract No. 1419-B327; IOVS; vol. 40;    No. 4; Mar. 15, 1999.-   Wolbarsht, M.; “Laser Surgery: CO.sub.2 or HF;” IEEE Journal of    Quantum Electronics; vol. QE-20; No. 12; pp. 1427-1432; December    1984.

SUMMARY OF THE INVENTION

The present invention, in some embodiments thereof relates to methodsand apparatus for treating high intra ocular pressure, using laserablation, and in particular, but not limited to, scanning regimes, laserparameters (optionally including laser type and/or wavelength), opticaldesign, post-operative treatment, reduction of scarring, aiming methodsand/or eye protection.

There is provided in accordance with an exemplary embodiment of theinvention, a method of ablating a scleral tissue, comprising:

-   -   providing a laser;    -   setting laser application parameters so as to provide minimal        thermally damaged tissue at a percolation layer above one or        both of a Schlemm canal and a trabecular meshwork of the eye;        and    -   activating said laser according to said parameters to achieve        said percolation, by ablating scleral tissue overlying said        percolation layer.

In an exemplary embodiment of the invention, said activating causes atleast twice as much thermal damage to walls of a carter formed by saidablation as to said percolation layer. Optionally or alternatively, saidactivating comprises targeting multiple areas with a short dwell time ateach and wherein said setting includes setting an overlap of at least20% between adjacent areas targeted by said laser. Optionally oralternatively, said setting comprises setting different parameters fordifferent depths of ablation. Optionally or alternatively, the methodcomprises applying both anti-inflammatory materials andanti-proliferation materials to said ablated area, in an amountsufficient to reduce scarring.

There is provided in accordance with an exemplary embodiment of theinvention, a method of non-penetrating filtration surgery on an eye,comprising:

-   -   (a) forming a flap in scleral tissue overlying a Schlemm canal        and/or a trabecular meshwork;    -   (b) ablating layers of said sclera with an ablation laser until        percolation is provided without macro-penetration to the eye;    -   (c) closing the flap; and    -   (d) needling in a space formed between said flap and said        ablated sclera.

In an exemplary embodiment of the invention, the method comprisesapplying a medicament in said space. Optionally or alternatively, themethod comprises selectively acutely reducing intra-ocular pressure bygonio-puncturing said eye. Optionally or alternatively, the methodcomprises topically applying cortisone to said flap or ablated sclera.Optionally or alternatively, the method comprises topically applyinganti-proliferation material to said flap or ablated sclera. Optionallyor alternatively, ablating comprises ablating with an overlap of between20% and 40% between adjacent ablation targets. In an exemplaryembodiment of the invention, ablating comprises ablating with a focusedCO2 laser set at between 20 and 30 watts. Optionally or alternatively,ablating comprises ablating with a dwell time at an ablation target ofbetween 200 and 400 microseconds. Optionally or alternatively, ablatingcomprises ablating with an ablation target diameter of between 200 and400 microns. Optionally or alternatively, ablating comprises ablating ashape with a concave portion following a curve of an iris or limbus orcornea of the eye. Optionally or alternatively, ablating comprisesablating a plurality of sub-portions of sclera underlying said flap.Optionally or alternatively, ablating comprises first ablating a first,larger area under said flap and then further ablating a sub area wheresome percolation is observed. Optionally or alternatively, ablatingincludes scleral tissue that is between 0.2 and 1.6 mm from the limbusof said eye. Optionally or alternatively, said flap is between 4 and 6mm wide and between 4 and 6 mm long and wherein said ablated areathrough which percolation is provided is between 1 and 5 mm long andbetween 0.5 and 3 mm wide, with width extending away from the limbus ofsaid eye. Optionally or alternatively, the method comprises determiningthat said ablation laser is in focus on said scleral tissue, byobserving the distance between two converging visible laser light spotswhich are directed at said scleral tissue. Optionally or alternatively,the method comprises mounting an eye protector on said eye, whichprotector prevents laser damage to tissue not under said flap.Optionally or alternatively, the method comprises adjusting a focallocation of said ablation laser by a transversely moving lens whichconverges said beam away from a beam combiner which combines saidfocused beam with a line of sight of a microscope, said transversemovement being relative to said line of sight.

In an exemplary embodiment of the invention, the method comprisesadjusting a position of said ablation laser by manually operating amicromanipulator. Optionally or alternatively, ablating comprisesenforcing a minimal wait of at least 1 or 2 seconds between consecutivemanually applied ablations.

There is provided in accordance with an exemplary embodiment of theinvention, a method of laser ablation of scleral tissue, comprising:

-   -   (a) targeting a laser at a first area overlying a Schlemm canal        and/or a trabecular meshwork;    -   (b) targeting said laser at a second area with an overlap of at        least 25% with said first area;    -   (c) targeting said laser at a third area in a direction        orthogonal to that of a line connecting said first and said        second areas, with an overlap of at least 25% with said first        area; and    -   (d) repeating (a)-(c) until percolation sufficient to reduce        intra-ocular pressure is achieved from said first, second and        third areas. Optionally, all of said overlaps are at least 30%.        Optionally or alternatively, said laser is targeted by scanning        and wherein said overlaps are uniform in substantially all of        said scan. Alternatively, said laser is targeted by scanning and        wherein said overlaps are not equal in substantially all of said        scan.

There is provided in accordance with an exemplary embodiment of theinvention, a method of laser ablation of scleral tissue, comprising:

-   -   (a) defining a target region for a laser as including a concave        portion following a limbus outer curvature;    -   (b) scanning a laser along said region, until percolation        sufficient to reduce intra-ocular pressure is achieved from said        target region. Optionally, scanning comprises scanning in        straight line paths. Optionally or alternatively, scanning        comprises scanning along curved paths.

In an exemplary embodiment of the invention, said target region isconvex in a direction away from said limbus.

There is provided in accordance with an exemplary embodiment of theinvention, a method of laser ablation of scleral tissue, comprising:

-   -   (a) defining a target region for a laser as including a region        at least 2 mm long and at least 0.5 mm wide and within a range        of between 0.2 and 1.6 mm from a limbus outer curvature;    -   (b) scanning a laser along said region, until percolation        sufficient to reduce intra-ocular pressure is achieved from said        target region. Optionally, said target region comprises a        plurality of disjoint portions within said range.

There is provided in accordance with an exemplary embodiment of theinvention, a method of laser ablation of scleral tissue, comprising:

-   -   (a) targeting a laser at a first area overlying a Schlemm canal        and/or a trabecular meshwork;    -   (b) ablating said first area using said laser;    -   (c) detecting a low level of percolation in a sub-portion of        said first area; and    -   (d) ablating said sub-portion until percolation sufficient to        reduce intra-ocular pressure is achieved from said sub portion.        Optionally, the method comprises separately ablating by        separately scanning with a laser a plurality of sub-portions of        said first area.

There is provided in accordance with an exemplary embodiment of theinvention, an eye protector, comprising:

-   -   a body adapted to be contacted with an eye; and    -   at least one IR blocking portion which has an optical density of        less than 0.4 for most visible light wavelengths and adapted to        block wavelengths that are well absorbed in water, with an        optical density of at least 0.9. Optionally, the protector        comprises a window that is transparent to wavelengths that are        blocked by said IR blocking portion. Optionally or        alternatively, said IR blocking portion also blocks red and/or        green wavelengths. Optionally or alternatively, said IR blocking        portion comprises at least 50% water.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation control system, comprising:

-   -   (a) a frame adapted for attachment to an ophthalmic microscope        and including a portion which is adjacent to a field of view of        said microscope;    -   (b) a beam combiner adjacent said portion and in the field of        view of said microscope;    -   (c) a beam scanner adjacent said portion and with an output        aimed at said beam combiner; and    -   (d) a converging lens between said scanner and said beam        combiner. Optionally, the system comprises a manual adjuster for        said combiner adjacent said combiner. Optionally or        alternatively, a focus of said scanned beam is found more than        130 mm from said beam combiner. Optionally or alternatively, a        depth of field of said scanned beam between 2 and 8 mm.        Optionally or alternatively, the system comprises an input for a        CO2 laser. Optionally or alternatively, the system comprises an        axial displacer adapted to control a distance between said lens        and said beam combiner. Optionally or alternatively, the system        comprises a plurality of locations for attachment of each of a        focal distance controller and a beam combiner manipulator.        Optionally or alternatively, the system comprises an adaptor        which couples said frame to said microscope. Optionally, said        frame includes at least protrusions:    -   (a) a first protrusion adapted to extend from said frame towards        said field of view and contact said adapter;    -   (b) a second, adjustable, protrusion adapted to cooperate with        said first protrusion and prevent removal of said frame from        said adapter; and    -   (c) a third, adjustable, protrusion adapted to lock said frame        to said adapter, when adjusted.

In an exemplary embodiment of the invention, the system comprises atleast two light sources positioned adjacent said lens and coupledthereto and aimed at said beam combiner and configured to have apredetermined spacing of light generated thereby at a focal length ofsaid lens.

In an exemplary embodiment of the invention, said system is mounted onan ophthalmic microscope.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation system, comprising:

-   -   (a) a frame adapted for attachment to an ophthalmic microscope        and including a portion which is adjacent to a field of view of        said microscope;    -   (b) a beam combiner in the field of view of said microscope;    -   (c) a beam scanner with an output aimed at said beam combiner;    -   (d) a converging lens between said scanner and said beam        combiner; and    -   (e) a linear displacement element adapted to modify a distance        between said lens and said beam combiner in a plane generally        perpendicular to a line of sight of said field of view.        Optionally, said linear displacement mechanism comprises a        micrometer screw.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation control system adapted for mounting on anophthalmic microscope, comprising a plurality of components including atleast a laser scanner which scans light in two dimensions, wherein saidplurality of components are configured for modular rearrangement.Optionally, said system is adapted for rearrangement in an operatingroom. Optionally or alternatively, at least one of said modules isadapted for reversal with respect to another module. Optionally oralternatively, at least one of said modules is adapted for attachment toa plurality of multiple locations on another of said modules. Optionallyor alternatively, at least two of said modules are configured to couplea light beam between the modules in an alignment set by mechanicalcoupling thereof.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation control system, comprising:

-   -   (a) a frame adapted for attachment to an ophthalmic microscope        and including a portion which is adjacent to a field of view of        said microscope;    -   (b) a beam combiner in the field of view of said microscope;    -   (c) a beam scanner with an output aimed at said beam combiner;    -   (d) a manipulator configured to adjust said beam combiner; and    -   (e) a focus controlling element adapted to modify a distance        between said frame and a focal point of said output, wherein,        each of said (d) and (e) has at least two possible mounting        points on said frame.

There is provided in accordance with an exemplary embodiment of theinvention, a system for mounting on an ophthalmic microscope,comprising:

-   -   (a) an adapter adapted for fixedly attachment to an ophthalmic        microscope and including a ring adapted to be located in a field        of view of said microscope;    -   (b) a frame adapted to mount on said adapter ring; and    -   (c) at least three protrusions on said frame, directed towards        said ring, including at least:        -   (i) a first protrusion adapted to extend from said frame            towards said field of view and contact said adapter;        -   (ii) a second, adjustable, protrusion adapted to cooperate            with said first protrusion and prevent removal of said frame            from said adapter; and        -   (iii) a third, adjustable, protrusion adapted to lock said            frame to said adapter, when adjusted. Optionally, said            second adjustable protrusion comprises at least two screws.            Optionally or alternatively, said first protrusion comprises            two protrusions and wherein third adjustable protrusion            comprises a screw which defines an equilateral triangle with            said two first protrusions.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation control system, comprising:

-   -   (a) a frame adapted for attachment to an ophthalmic microscope        and including a portion which is adjacent to a field of view of        said microscope;    -   (b) a beam combiner in the field of view of said microscope;    -   (c) a beam scanner adjacent said portion and with an output        aimed at said beam combiner;    -   (d) a converging lens between said scanner and said beam        combiner; and    -   (e) at least one patterned light sourced fixedly coupled to said        lens and aimed at said beam combiner, which light source        generates a pattern having a pre-determined form at a focal        location of said output. Optionally, said at least one patterned        light source comprises at least two point sources, generating a        converging pair of rays which converge at said focal location.        Optionally, the at least two point sources are each mounted        within 5 cm from a center of said lens and on opposite sides        thereof. Optionally or alternatively, the at least two point        sources are each mounted within 3 cm from a center of said lens.

In an exemplary embodiment of the invention, said beam combinercomprising a path folding mirror configured to be transparent to mostwavelengths of visible light and configured to reflect both ablationwavelengths and said patterned light. Optionally or alternatively, thesystem comprises a focus adjusting element adapted to move said lenstogether with said patterned light source to change a distance of saidlens from an eye. Optionally or alternatively, said frame is adapted torotate relative to said microscope. Optionally or alternatively, saidbeam combiner is positioned at a side of said field of view of said beamscanner.

In an exemplary embodiment of the invention, the system comprises amicromanipulator adapted for manual adjustment of said beam combiner.

There is provided in accordance with an exemplary embodiment of theinvention, a method of laser ablation focus indication, comprising:

-   -   (a) providing a laser beam suitable for tissue ablation;    -   (b) focusing said laser beam using at least one lens having a        focal length; and    -   (c) aiming a plurality of beams from said lens and adjusted to        converge at said focal length. Optionally, aiming comprises        adjusting said beams to provide said convergence. Optionally or        alternatively, the method comprises folding said laser beam and        said plurality of beams using a same mirror. Optionally, said        mirror is at least partially transparent and found in a viewing        field of an ophthalmic microscope.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation control system, comprising:

-   -   (a) a card reader;    -   (b) a laser beam controller;    -   (c) circuitry configured to control one or both of said laser        beam controller and a laser beam source in accordance with data        read by said card reader to perform ablation suitable for        non-penetrating filtration surgery on an eye. Optionally, said        circuitry prevents a firing of an ablation laser by said laser        beam controller. Optionally or alternatively, said circuitry        prevents a scanning of an ablation laser by said laser beam        controller. Optionally or alternatively, said circuitry limits a        time of activation of said controller. Optionally or        alternatively, said circuitry limits a number of activations of        said laser beam controller or said laser beam source. Optionally        or alternatively, said circuitry controls said controller with        ablation parameters suitable to ablate a thickness of scleral        tissue, according to said data. Optionally or alternatively,        said circuitry allows reuse of a card and debts a later read        card.

There is provided in accordance with an exemplary embodiment of theinvention, a method of controlling laser ablation, comprising:

-   -   (a) reading a card by an ablation system; and    -   (b) enforcing both a number of ablation steps and a duration of        activation of said system in an ablation mode, according to data        read by the ablation system.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation control system, comprising:

-   -   (a) a laser beam controller;    -   (b) a manual triggering mechanism for triggering said        controller; and    -   (c) circuitry configured to prevent triggering of said        controller within a repeat delay time of at least 0.5 seconds        since a previous triggering.

There is provided in accordance with an exemplary embodiment of theinvention, a method of controlling laser ablation, comprising:

-   -   (a) ablating using a first ablating step; and    -   (b) automatically preventing a second ablation step from        occurring within a repeat delay time of at least 0.5 seconds        since said ablating.

There is provided in accordance with an exemplary embodiment of theinvention, a laser ablation system, comprising:

-   -   (a) a laser beam controller;    -   (b) a laser source; and    -   (c) circuitry configured to drive said controller with        parameters suitable for removal of scleral tissue in a thickness        of at least 10 microns and which avoid thermal damage of a        thickness of more than 30 microns, in a layer of percolating        scleral tissue. Optionally, said removal is by thermal        vaporization. Optionally or alternatively, said parameters cause        thermal damage of at least 50 microns in thickness in an upper        layer of scleral tissue. Optionally or alternatively, a radio        between thickness of thermal damage between said percolating        layer and said upper layer is at least 1:5. Optionally or        alternatively, said thickness beyond which damage is avoided is        less than 20 microns in thickness. Optionally or alternatively,        said circuitry is also configured to drive said controller with        parameters which cause thermal damage in a thickness of at least        30 microns in said layer of percolating scleral tissue.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

Implementation of the method and/or system of embodiments of theinvention can involve performing or completing selected tasks manually,automatically, or a combination thereof. Moreover, according to actualinstrumentation and equipment of embodiments of the method and/or systemof the invention, several selected tasks could be implemented byhardware, by software or by firmware or by a combination thereof usingan operating system.

For example, hardware for performing selected tasks according toembodiments of the invention could be implemented as a chip or acircuit. As software, selected tasks according to embodiments of theinvention could be implemented as a plurality of software instructionsbeing executed by a computer using any suitable operating system. In anexemplary embodiment of the invention, one or more tasks according toexemplary embodiments of method and/or system as described herein areperformed by a data processor, such as a computing platform forexecuting a plurality of instructions. Optionally, the data processorincludes a volatile memory for storing instructions and/or data and/or anon-volatile storage, for example, a magnetic hard-disk and/or removablemedia, for storing instructions and/or data. Optionally, a networkconnection is provided as well. A display and/or a user input devicesuch as a keyboard or mouse are optionally provided as well.

BRIEF DESCRIPTION OF THE DRAWINGS

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and for purposes of illustrativediscussion of embodiments of the invention. In this regard, thedescription taken with the drawings makes apparent to those skilled inthe art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a picture of a beam manipulation system (BMS) mounted on anophthalmic microscope (OM) and connected to a laser source using anarticulated arm, in accordance with an exemplary embodiment of theinvention;

FIG. 2 is a picture of a beam scanning portion and focusing sub-systemof the device of FIG. 1, in accordance with an exemplary embodiment ofthe invention;

FIG. 3A and FIG. 3B illustrate the attachment of a beam combiner andmicromanipulator together with the beam scanning portion of FIG. 2, withan optional focus controller, in accordance with an exemplary embodimentof the invention;

FIG. 4A is a cross-sectional view and FIG. 4B is an isometric view ofthe micromanipulator, the beam combiner and the beam scanner of FIG. 3,with FIG. 4B also showing an adapter, in accordance with an exemplaryembodiment of the invention;

FIG. 5 is a schematic showing of a coupler for attaching the elements ofFIGS. 3-4 to a microscope, in accordance with an exemplary embodiment ofthe invention;

FIGS. 6A-6D illustrate various configurations of a BMS, in accordancewith an exemplary embodiment of the invention;

FIGS. 7A-7D illustrate optional scan paths that generally conform to theshape of a limbus, in accordance with an exemplary embodiment of theinvention;

FIG. 8 is a flowchart of a method of treating an eye, in accordance withan exemplary embodiment of the invention;

FIG. 9 is a schematic top view of a design of an alternative BMS, inaccordance with an exemplary embodiment of the invention;

FIG. 10 is a chart showing experimental results for a device inaccordance with the alternative design of FIG. 9.

FIG. 11A and FIG. 11B are images of cross-sectional views in eyes,showing different amount of thermal damage for different laser settings,in accordance with an exemplary embodiment of the invention;

FIG. 11C schematically illustrates different amounts of thermal damagein different parts of an ablation crater in accordance with an exemplaryembodiment of the invention;

FIG. 12 shows an exemplary overlap in two dimensions between treatmentspots, in accordance with an exemplary embodiment of the invention;

FIG. 13 is a chart showing reduction in intra-ocular pressure inpatients treated in accordance with an exemplary embodiment of theinvention;

FIG. 14 is a chart showing reduction in drug usage in patients treatedin accordance with an exemplary embodiment of the invention;

FIG. 15 is a chart showing a comparison between different sites atdifferent geographical locations and different surgeons where patientswere treated in accordance with an exemplary embodiment of theinvention; and

FIG. 16 is a chart showing complete and qualified success rates forpatients treated in accordance with an exemplary embodiment of theinvention.

DESCRIPTION OF EXEMPLARY EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof relates to methodsand apparatus for treating high intra ocular pressure, using laserablation, and in particular, but not limited to, scanning regimes, laserparameters, optical design, post-operative treatment, reduction ofscarring, aiming methods and/or eye protection.

An aspect of some embodiments of the invention relates to ease of use ofa laser ablation system in accordance with exemplary embodiments of theinvention. In an exemplary embodiment of the invention, a distancebetween the system (e.g., a scanning ablation source and a microscope)and the eye is at least 10, 15, 20 or more centimeters. Optionally, thisdistance allows a physician to place his hands between themicroscope/scanner and an eye, without touching the microscope and/ormaximizes the available free space as dictated by the optics of theophthalmic microscope. In an exemplary embodiment of the invention, suchdistance is provided by providing a beam combiner for reflecting laserlight from a source thereof at an entrance of said laser light into afield of view of the microscope. It should be noted that such design maybe more complex than providing the combining at a far side of the fieldof view, as if the beam combiner is adjustable, such design may causemechanical interference between an adjustment mechanism for adjustingthe beam combiner and the laser source. In an exemplary embodiment ofthe invention, separation is provided by changing the focal length of alens focusing the ablation laser. Optionally, however, the lens focallength is selected to match the microscope focal length.

In an exemplary embodiment of the invention, adjustment of the beamcombiner is used to precisely locate the ablation region on the eye.Optionally, for example as described below, adjustment includestranslation (in one or two dimensions) and rotation. Optionally, anaiming beam is used to indicate a location where a flap is to be cut.This may allow the entire procedure to be under the guidance of thesystem.

Optionally or alternatively, the optics of the laser source are set upso that a significant depth of field of operation is provided, forexample, 3, 4, 5, 6 or more mm. In an exemplary embodiment of theinvention, such depth of field is provided by using a low-diopterfocusing lens for the laser source (optionally more than one lens isused). Optionally, the laser source is a CO2 laser. Other lasers may beused, but this may affect the desired dwell times and/or spot sizes. Forexample, a laser which removes less tissue at a given time period may beprovided with a shorter dwell time or an increased number of automaticrepetitions, so that a desired thickness (e.g., 5-50 microns) isremoved. In some cases, the spot size and dwell time or laser pulse timeare determined by the type of laser-tissue interaction (e.g., requiredenergy density).

Optionally or alternatively, the position of the operational fieldrelative to the microscope is moved using a micrometer and withoutmoving the ablation system portions that are mounted on the microscope(e.g., the scanner and/or beam combiner are not moved relative to themicroscope). In an exemplary embodiment of the invention, the scanner ismoved and the beam combiner and optional micromanipulator are not moved.This may allow repositioning when the microscope head with the system onit and/or the patient are moved for any reason during a procedure orbetween procedures. In an exemplary embodiment of the invention, themicrometer moves a focusing lens of the scanned laser beam towards oraway from the microscope and a beam-combining reflecting mirror, therebythe micrometer changes the optical distance between the laser source andthe eye being treated. In some embodiments, for example, as noted above,the lens is moved with the scanner.

In an exemplary embodiment of the invention, the repositioning of theoperational field (and/or its width) of the laser is carried out toprovide and/or maintain an alignment between the optics of the laser andthe optics of the microscope. This may allow better monitoring of thetissue being ablated, as the focal planes of the laser (ablation) andthe microscope (monitoring) would be aligned.

In an exemplary embodiment of the invention, the beam combining mirrorcan be adjusted manually (e.g., act as a micromanipulator).

Optionally or alternatively, a focus aiming system with a pattern isprovided, which pattern indicates if the treated surface of the eye iswithin the operational depth of field. In an exemplary embodiment of theinvention, the focus aiming system comprises a plurality of separatevisible laser sources, which are aimed to converge and/or cross andoptionally do not share the focusing optics of the ablation source.Rather, the sources are designed to converge/cross and/or be within aknown (optionally small) distance from each other, at the operationalfield. In an exemplary embodiment of the invention, the combining mirroris sized and made of materials suitable to reflect the focus aimingbeams as well, while minimizing interference with the microscope.Optionally, each focus aiming laser has a focusing lens having a focallength similar to that of the focusing lens of the ablation laser (e.g.,to the point of expected convergence of the two beams). In an exemplaryembodiment of the invention, the focal length of the focus laser(s) isadjusted to converge on the tissue—according to its location in thedesigned system. Optionally, such focusing lenses serves to improveaccuracy of the focusing sub-assembly In an alternative embodiment thetwo lasers share the lens with the ablation laser, albeit, this maydepend on the wavelength involved and available space.

Optionally or alternatively, an aiming beam for indicating the ablationlocation and/or flap formation location is coaxial with the ablationlaser beam and shares a significant part of the optical path thereof.Such an aiming beam may be scanned with the ablation laser, for exampleif it is optionally combined with the ablation laser beam beforescanning, rather than after scanning.

An aspect of some embodiments of the invention relates to reducingscarring and/or thermal damage (which may promote scarring). It has beensurprisingly been discovered by the inventors that laser settings whichcause significant thermal damage when ablating scleral tissue, can beselected to cause substantially no or very reduced thermal damage (e.g.,over at least 70%, 80%, 90% of the area) at a layer of sacral tissueadjacent the Schlemm canal and/or trabecular meshwork. Optionally, theparameters of ablation are modified as the ablation depth increases andapproaches the level of the Schlemm canal. Alternatively, the ablationparameters are selected to be optimal for the areas adjacentpercolation. In an exemplary embodiment of the invention, the ablationparameters, including, for example, overlap between adjacent ablatedareas, power and/or dwell time are selected so as to make use of thethermal mass provided by percolating fluid. Optionally, thermallydamaged tissue is ablated and new tissue not damaged, as the percolatinglayer is reached, with heat being transported by the percolating fluid,which can serve as a very large heat sink. Optionally or alternatively,the laser layer of scleral tissue is not thermally damaged as it isprotected by such a thermal sink and/or percolating fluid. Optionally,the time delay until a same location is ablated is set so that such aprotected layer can be protected by new percolation. Optionally, suchpercolation is seen by an operator (and/or an automated system) and usedas a signal to stopping the procedure.

In an exemplary embodiment of the invention, scleral tissue is assumedto vary in that it has different thermal relaxation times (TRT). Thus,for example, to reduce thermal damage for a lower TRT tissue, highersource power, shorter dwell times and/or smaller spot sizes may beneeded. Optionally, however, tissue which is or near at a percolationlayer, includes a significant percentage of water, providing, forexample, a larger thermal sink (e.g., possibly also in adjacent tissue)and/or a longer thermal relaxation time, thus allowing a longer dwelltime and possibly a lower power density to achieve a desired amount ofthermal damage. Using such settings at a higher scleral layer mightcause significant thermal damage, due to the dwell time being longerthan the TRT of the higher layer. In an exemplary embodiment of theinvention, the laser parameters are matched to the TRT of the tissue tobe ablated and/or to other properties thereof, such as thermal capacityand evaporation point and/or material disassociation point. Optionally,the matching is to tissue which is at least 70%, 80%, 90% orintermediate percentages by volume of water.

In an exemplary embodiment of the invention, thermal damage thickness atthe lowest layer of the sclera is less than 50 micron, 40 micron, 30microns, 20 microns or 10 microns (over most of said area, for example,over 80% thereof), optionally being invisible. Optionally oralternatively, the ratio between thermal damage thickness at the lowestlayer and at the highest layer is a factor of at least ×2, ×4, ×6, ×10or intermediate factor. Optionally, the system is preconfigured withlaser ablation settings optimized for minimal damage at the lowestscleral layer, even if such settings cause considerable damage at higherlayers. Optionally or alternatively, the system is programmed also withlaser parameters suitable for minimizing and/or reducing thermal damageto upper layers of the sclera. This may be useful, for example, toensure that if a two step ablation procedure is performed, with some ofthe sclera ablated to percolation and some not, that there is reduceddamaged tissue which may cause scarring.

In some embodiments of the invention, a certain, measured amount ofthermal damage and/or leftover char material is desired, as a means ofpreventing adhesions and/or preventing full healing (either of which mayreduce percolation) and/or otherwise preventing of percolationreduction. Optionally, this amount is, for example, between 5 and 50microns thick, for example, between 10 and 30 microns thick.

In an exemplary embodiment of the invention, adjacent laser ablationtargets are selected to overlap by, for example, 10%, 20%, 30%, 40% ormore, of the diameter of the focused beam (e.g., for uniformly shapedtargets, the distance between target centers is for example, 30% lessthe target extent in the direction connecting the two target centers).In an exemplary embodiment of the invention, the overlap is provided intwo orthogonal directions. Optionally, the overlap is not uniform, forexample, being greater or smaller as the ablation processapproaches/overlies the Schlemm's canal. In some cases, overlap betweenadjacent scan lines (and time between consecutive and/or overlappingablations) is also taken into account when determining the energydeposition per time unit as being enough to ablate before heat leaksaway (e.g., to adjacent tissues), and/or not being too high.

Overlap may be useful to compensate for a non-uniform powercross-section of the beam. Typically, beam intensity is Gaussian incross-section (though other non-uniform patterns may be used as well),meaning that the edges of the target may receive less power than thecenter. Overlapping can correct this imbalance of power deposition. Insome embodiments, the beam cross-section is selected so that a circularbeam with suitable overlap can provide substantially uniform energydeposition (e.g., within a factor of 2 or 3).

In an exemplary embodiment of the invention, the ablation parameters,including overlap are selected so that areas with too high an overlapfactor are not overly thermally damaged, while areas with no overlap orpossibly no direct beam contact, if any, receive enough energy fromadjacent target areas, to be ablated. Optionally, the overlap isselected so that border regions of a target receive enough energy (e.g.,from two or more targeting events), to overcome any heat loss due toconduction, which loss might prevent proper ablation.

In an exemplary embodiment of the invention, additional parameters arevaried, for example, dwell time is reduced, for example, to 300-500microseconds (e.g., 320) and pulse power is increased, for example tobetween 18 and 50 watts (e.g., 24). Optionally, this keeps the depositedenergy the same, and may allow the dwell time to be shortened, possiblybelow thermal relaxation tine. Other dwell times, for example, between 1microsecond and 300 microsecond (possibly suitable for short pulselasers) or between 500 and 1000 microsecond, may be used. By dwell timeis meant the amount of time that the laser is aimed at the tissue in acertain location, even if the power output of the laser (on the tissue)is low or zero at the time. Tissue interaction time is typically shorterfor pulsed and/or shuttered lasers, and is the sub-portion of timeduring which the laser is aimed at the tissue and powered.

In an exemplary embodiment of the invention, the dwell time or ablationrepetition time is made longer (or shorter) than a tissue thermalrelaxation time, according to the desired effect. Optionally, therelaxation time in soft tissues is taken to be between 0.5 and 0.7 or 1milliseconds and the dwell time and/or tissue interaction time and/ortime between repeated pulses to a same location is made shorter thereof.In an exemplary embodiment of the invention, a parameter that isselected is the laser wavelength and/or laser type. Optionally, this isby replacing the laser and/or tuning a tunable laser. Optionally oralternatively, laser parameters are changed so as to change thelaser-tissue interaction, for example, selecting between vaporization,vaporization and then tissue particles ejection by the pressure of thevaporized tissue, molecular disassociation, photo-disruption, and othernon-thermal photo-ablation of tissue. It should be noted that changinglaser often changes the amount of tissue removal for each ablation,which may be compensated for by automated repeated ablation at a samepoint a predetermined number of times, calculated to achieve a desiredremoval amount in a removal step.

In an exemplary embodiment of the invention, the beam is maderectangular, optionally to promote more uniformity in overlap.

In an exemplary embodiment of the invention, when using laser ablation,for example, as described herein, scarring is reduced and/or proceduresuccess increased by needling, a processes wherein a needle or otherthin sharp object is placed in the ablation crater and moved around todisengage any adhesions which may have formed with the flap.

Optionally or alternatively to needling, pressure is temporarily reducedin the eye, using a goniopuncturing of the eye. Such pressure reductionand/or needling is optionally applied after the ablation procedure iscompleted, for example, after a few days (e.g., 2-5 days), weeks (e.g.,1-4) or months (e.g., 2-10), possibly after 1 or more years.

In an exemplary embodiment of the invention, needling and/orgoniopuncturing is applied when percolation is slowed down, for example,due to adhesions and/or other adverse physiological conditions. Suchpuncturing should be distinguished from penetration into the eye, oftencharacterized by a large hole and/or tear which is large enough causeiris prolapse.

Optionally or alternatively, the ablated area is treated withanti-inflammatory materials, steroid and/or non-steroid.

Optionally or alternatively, the ablated area is treated withanti-proliferation materials.

Optionally, the space between the ablated area and the flap is filledwith a spacer/implant, optionally biodegradable, viscoelastic materialsuch as Healon5, which optionally dissipates after a while (e.g., 5-20days, 1-3 weeks or 2-3 months or year). Alternatively, the spacer and/ormaterial stays in the eye indefinitely.

Optionally or alternatively to treatment immediately after the ablation,treatment is continued for several days or weeks thereafter.

In an exemplary embodiment of the invention, pressure-reducing drugs arestopped after a few days or weeks. Optionally or alternatively,intra-ocular pressure goes down to below-pathological levels.

Some such methods may also be applied to non-laser non-penetratingfiltration surgery.

An aspect of some embodiments of the invention relates to scanparameters. In an exemplary embodiment of the invention, the scan shapeis defined to include a concave section, optionally selected to match acurvature of a limbus of the eye. In an exemplary embodiment of theinvention, this scan path is chosen so as to ensure ablation over theSchlemm canal, which is found within 0.2-1.6 mm from the limbus.Optionally or alternatively, the scan path (e.g., and the ablationregion) is otherwise shaped to include some or all of the regiondistanced between about 0.2 and 1.6 mm from the limbus, along thescleral tissue layer.

It should be noted that the position of the limbus changes as a functionof the depth into the sclera. Optionally, the positioning of theablation region is changed based on the actual thickness of flap that iscut (e.g., thereby determining the limbus position).

In an exemplary embodiment of the invention, the scan is carried outusing curved movements of the beam, for example, movements along linesthat are parallel to the concave section. Optionally, the part of thescan distal from the limbus is convex. Optionally or alternatively, thescan path is using straight raster lines. Optionally or alternatively,the distal part of the scan is straight, rather than concave.

In an exemplary embodiment of the invention, the scans overlap,optionally with a uniform overlap.

In an exemplary embodiment of the invention, a two step scanning processis used. In a first step, an entire region is scanned, for example,about 3 by 6 mm. Then, note is taken of where some percolation is found.Optionally, this indicates the position of the Schlemm's canal buriedwithin the Sclera layer. A second ablation step is carried out only inthe area, or in a fixed scan shape including the area, where there ispercolation.

In an exemplary embodiment of the invention, an ablation area issubdivided into sub-areas, each one being ablated separately, possiblyto a different depth.

In an exemplary embodiment of the invention, the flap which is preparedbefore the ablation is considerably larger than the planned first(and/or second) ablation areas, for example, being 1-2 mm larger inextent in 1, 2, 3, or 4 cardinal direction compared to the ablationarea. The flap may have up a large circumferential length (e.g.,parallel to the limbus—of 5, 6 or 7 mm). Optionally, the longer thelength the better in terms of having large percolation area.

In an exemplary embodiment of the invention, controlling software and/orcircuitry of the ablation system is set up to include two ablationpattern sizes, optionally with different ablation parameters (e.g., withdifferent optimizations for thermal damage). Optionally, the system isprovided with a control, for example, a button, which determines whichsize and/or other, optionally predetermined, settings are used.Optionally, the button has only two settings. Alternatively, additionalsettings are provided, such as 3 or 4. Optionally, the control is afoot-pedal or is adjacent or mounted on the micromanipulator controls.

An aspect of some embodiments of the invention relates to an eyeprotector (e.g., for protecting corneal/scleral tissue and/or internaltissues such as a retina). In an exemplary embodiment of the invention,the eye protector is mounted on the cornea and/or also beyond it andincludes a window (e.g., or a notch) for passing the ablation laser andaiming light wavelengths at the region of the flap. Optionally oralternatively, outside of the window, the ablation light and,optionally; the aiming light are blocked (e.g., 90%, 95%, 98% or 99.9%blockage) by the protector. In an exemplary embodiment of the invention,the protector is a high-water content gel, for example, with more than40% water content. Alternatively or additionally, other materials whichabsorb the specific laser radiation, even if they have no water content,may be used. Optionally, a material is chosen which does not emit toxicand/or hot particles or fluids when hit by the ablation laser.Optionally, the protector is a contact lens with an aperture or othershape (e.g., depression or optics-affecting treatment) formed therein.Optionally, the protector is shaped to cover the cornea and/or includesextensions radially extending on either side of the planned ablationarea to prevent inadvertent ablation outside the planned region.

In an exemplary embodiment of the invention, the protector is designed(e.g., thickness) to properly function for only a small number ofablations, for example, 1, 2, 3 or between 4 and 10 ablation acts, orthe number of ablation acts allowed or expected in a procedure.

In an exemplary embodiment of the invention, the protector istransparent to visible light or at least to parts of the visiblespectrum substantially everywhere, so a physician can view the eyethrough it.

In an exemplary embodiment of the invention, the protector is opaque tovisible light or at least to parts of the visible spectrum, optionallysubstantially for its entirety, so the visible laser cannot pass throughit.

An aspect of some embodiments of the invention relates to ease ofmounting of the laser ablator on an ophthalmic microscope. In anexemplary embodiment of the invention, an adaptor is provided to fix theablator to a microscope. Optionally, the adapter attaches to themicroscope using standard methods (e.g., screws at standard locations).

In an exemplary embodiment of the invention, the ablator is coupled tothe adapter with two types of mountings, a first type for providingcoupling but optionally allowing rotation of the ablation system aroundthe optical axis of the field of view, and a second one for providingrigidity. Optionally, rotation is used to align the ablation shape withan actual flap formation location.

In an exemplary embodiment of the invention, trans-axial (to microscopeaxis) alignment is provided using a hierarchy of connection methods. Inan exemplary embodiment of the invention, an aperture of the ablatormounts on a ring of the adapter, which is itself aligned with themicroscope. In an exemplary embodiment of the invention, a plurality ofscrews extend into said aperture and against said ring. Optionally,first plurality of screws (or fixed protrusions) define two points of atriangle (or other geometry). A second plurality of screws (or singlescrew), optionally symmetric with respect to the axis of the triangle,may be used for ensuring that the ablator cannot fall off the adaptor,for example, if the adaptor ring has a lip (or a groove or one or moredepressions) and the shape defined by the screws has a minimum diametersmaller than that of the lip (or matching the groove and/ordepressions). A third screw or screws, optionally symmetric with respectto the shape, is used for fixing the aperture to the ablator, byfriction, optionally retarding and/or preventing rotation thereof.

In an exemplary embodiment of the invention, the scanning system isprovided as multiple (e.g., 2, 3, 4, 5, 6 or more) modular componentswhich can optionally be easily (e.g., in an OR or other non-workshopsetting, e.g., using a standard tool such as a screwdriver or hexwrench) rearranged for various mounting situations and/or have partsreplaced for different situations. In one example, the adapter is aseparate element which may be matched to a particular microscope design.In another example, a beam scanner and a beam combiner may be coupled ina plurality of manners to match geometrical considerations. Optionally,the beam combiner is designed to mount in both a normal position and aflipped position on a microscope/adapter, for example, by using a mirrorwhich is reflected on both sides.

Optionally, at least two of the modules have their own separatehousings. Optionally, at least one module can be reversed with respectto another module for attachment thereto. Optionally, at least twomodules share this ability to be reversed in assembly.

In an exemplary embodiment of the invention, the scanning system isdesigned to include multiple positions for attaching one or more of usermanipulation controls, for example, a beam combiner adjuster and fieldlocation adjustor. In an exemplary embodiment of the invention, suchmanipulation controls may be positioned in a location where theirphysical presence does not interfere with other tools in the operatingspace, while preserving their functionality.

An aspect of some embodiments of the invention relates to an enforceddelayed (also termed herein “repeat delay”) between repeated ablation ofa same location. In an exemplary embodiment of the invention, theablation procedure comprises repeated ablations, with each ablationremoving, for example, 5-50 microns or some other desired amount.Optionally, initial ablations are thicker than later ablations or thesystem includes a button to select ablation depth. It should be notedthat for some laser parameter settings and lasers, a desired ablationdepth is achieved by repeated ablation of a same point. However, oncesuch a desired ablation depth is achieved, it is generally desirable tovisually inspect the eye (or some other means) to determine ifpercolation has started and/or is sufficient. In some cases, a user mayinadvertently apply a second ablation before such checking and/or maynot wait long enough to see the effects of ablation, to see percolationand/or to allow the self-limiting protective feature caused bypercolation to come into action. In an exemplary embodiment of theinvention, the ablation system enforces a minimal delay. In one example,the trigger mechanism includes electronics (e.g., a capacitor circuit)which does not accept a second pressing of the trigger if a desireddelay (e.g., preset to 1-3 seconds or user settable) has not passed.Optionally or alternatively, such a delay is enforced using a mechanicalmeans, for example, a slow return on the trigger to an “armed position”and/or by a safety being automatically engaged. Optionally oralternatively, such a delay is enforced using computer control, whichmeasures time. Optionally, the delay is determined, at least in part onthe number and/or position of ablation repetitions so far. Optionally oralternatively, the total number of ablations is limited, to preventinadvertent damage to the eye (e.g., shock damage) which may be causedby continuous ablation of a percolation layer.

An aspect of some embodiments of the invention relates to control of theusage of the ablation system. In an exemplary embodiment of theinvention, a card is provided which is precharged with usage parametersand optionally ablation parameters. Optionally, such a card is a smartcard, a memory card, an RFID and/or a bar-code or other computerreadable media. In an exemplary embodiment of the invention, theablation system includes a suitable card reader. Optionally, the cardincludes the information encoded thereon. Optionally, the card iswritable and can be written by the ablation system (e.g., using thereader). Optionally or alternatively, the card includes a code which isused to access the information, for example, information stored in thesystem or available by a network connection.

In an exemplary embodiment of the invention, the card includes thereonor links to one or more of:

-   -   (a) card ID;    -   (b) device ID;    -   (c) times at which devices are allowed to be or were (e.g., for        a writable card) activated; and    -   (d) procedure parameters (e.g., one or more of laser parameters,        number of ablation steps allowed (e.g., parameter being between        4 and 25 or 100), ablation thickness (e.g., between 5 and 75        microns), repeat delay (e.g., between 1 and 4 seconds), allowed        pause (e.g., time after which it is assumed that a procedure was        stopped, for example, a value between 3 and 7 minutes) and total        procedure time (e.g., a value between 10 and 30 minutes)).

Optionally, a card is provided for one procedure. In other embodiments,a card supports multiple procedures.

In an exemplary embodiment of the invention, a procedure cannot bestarted without a card being read and/or being inserted in a reader.Optionally, the card controls the turning on of the laser and/or ashutter which allows passage of laser light to the scanner. In anexemplary embodiment of the invention, the time of the procedure ismeasured from when the ablation laser is turned on (e.g., via the systemor manually and then sensed), or from a first or second ablation step.Optionally or alternatively, the scanner will not operate without thecard. In an exemplary embodiment of the invention, an aiming beam isprovided and does not count as part of the procedure time. When theallotted time is up or when the allowed number of ablation stepperformed, the card is deactivated and the procedure cannot continue.This can be used as a safety feature to avoid over ablation. Optionally,a safety feature is provided in that if a procedure is prematurelyterminated due to card logic for some reason, removing and inserting thecard (optionally only the same card) will allow an additional time spanand series of shots. Optionally, this time is a loan and is recouped bycanceling of the next inserted card without allowing a procedure to beperformed.

Optionally, the cards are used to control billing, with each card beingsold for a fixed sum and/or a particular device and/or procedure (e.g.,a card scheme can also be used for other laser based procedures).

In an exemplary embodiment of the invention, a range of cards areprovided. For example, a “factory card” can be used in an unlimitedmanner. A technician card may, for example, read form the device thepast usage log and/or require changing of a site and/or device betweenreuses. A test card is optionally provided, for example, for daily orother testing of the system. Optionally, testing is on a blank, forexample, Type “Classic Crest” made by Neenah Paper Inc. (Alpharetta,Ga., USA) In an exemplary embodiment of the invention, the test cardcauses the system to generate a pattern which is unsuitable for thedesired procedure, for example, including a correctly shaped test area,with adjacent ablation areas, which, in a human eye would, for example,overlie the cornea. Optionally, the testing shows if a correct amountand shape of tissue will be ablated when the system is in use.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not necessarily limited in itsapplication to the details of construction and the arrangement of thecomponents and/or methods set forth in the following description and/orillustrated in the drawings and/or the Examples. The invention iscapable of other embodiments or of being practiced or carried out invarious ways. In particular, various aspects and features of theinvention may be practiced in conjunction with scleral ablation systemsor other eye and/or laser treatment systems other than the OT-134 andOT-133 and variants thereof described in greater detail below.

Overview of OT-134 Embodiments

Referring now to the drawings, FIGS. 1-6D illustrate components,subcomponents and assemblies of a laser ablation control system (LACS),in accordance with an exemplary embodiment of the invention. Variousfeatures, options and alternatives are also discussed below. The system,adapted for mounting on an ophthalmic microscope or being made integralwith one, generally comprises a source of a scanned laser beam and abeam combiner for combining with a line of sight of a microscope. In anexemplary embodiment of the invention, the scanned beam is focused.Optionally, an aiming pattern source is provided. Various adjustment andcoupling mechanisms are optionally provided. It is a particular featureof some embodiments of the invention, that the LACS is distanced fromthe focal location of the laser beam by at least 130-170 mm, allowingfor a physician to easily pass a hand between the eye and the LACS,without accidentally contaminating the LACS and/or moving it. It is aparticular feature of some embodiments of the invention that the LACScan be easily adjusted so that the ablating laser beam is in focus onthe target.

In addition, described below are various ablation parameters. It shouldbe noted that such parameters may be applied with systems other thandescribed herein.

OT-134 Beam Manipulating System—General Description

The LACS includes a Beam Manipulating System (BMS) and a controller (notshown), for example, a computer with a display, which controls the BMS.Optionally or alternatively, the BMS includes an onboard controllingcircuit. In an exemplary embodiment of the invention, the controller isprogrammed for and/or accepts user input, to drive the BMS to performvarious scan paths and/dwell times. Optionally, the controller isprogrammed to prompt a user (e.g., using an audio, including optionallyspeech and/or a visual reminder) what is a next step to perform during aprocedure. Optionally, also not shown, LACS includes a vision system(e.g., a camera and an image processor) which views the treated area andprovided feedback, optionally automated, optionally to a user forexample, on correct focusing of the laser and/or positioning withrespect to the cornea or other landmark of the eye. Methods foridentifying the cornea and/or visible laser beams are known in the artand may be used for this. Optionally, the vision system views throughthe microscope. Alternatively, the vision system is mounted (e.g., onthe microscope or patient or bed), possibly without exact calibration,so long as it views the treated area. Optionally, such feedback may, butneed not, include feedback on starting of percolation or of sustainedfunctional percolation.

FIG. 1 shows a BMS 174 mounted in configuration 170 for use. The BMS isan opto-mechanical system which is used to ablate tissue in conjunctionwith a CO₂ laser and (optionally) a microscope 106 (an optional secondviewer 172 is also shown). The BMS receives as input laser beam,optionally a static laser beam, for example one exiting from thearticulated arm of a medical grade CO₂ laser system 100. In otherembodiments, the controller also controls the laser source, for example,its power and/or intrinsic pulse or other temporal parameters.

A brief overview of the figures; FIG. 1 shows the complete BMS inoperation; FIGS. 2-3B show sub-assemblies; FIG. 4A is a cross-sectionalview of the BMS; FIG. 4B is an isometric view; FIG. 5 shows an optionaladapter component; and FIGS. 6A-6D show various configuration options.

A main BMS 174 scans the beam in a raster pattern in, for example,shape, dimensions, raster scan speed, raster density and/or positionand/or orientation on the eye tissue, which can be selected andcontrolled by the user. The scanned beam is then focused with a focusinglens (101, FIG. 4A) onto the treated tissue.

In the depicted embodiments (e.g., the OT-134 beam manipulating system),the 4 following sub-systems are provided:

1. Scanner

A beam scan mechanism 102 is used to create the raster pattern at presetshape, size, and the scanning parameters of the laser beam on the tissueas determined by the user. The scanner is driven by the controller (notshown).

2. Beam Combiner and Micromanipulator

A beam combiner and micromanipulator (MMP) 109 connects the OT-134system to the ophthalmic microscope (OM, 106), optionally using anadaptor (e.g., 103, below), allowing the physician to use the OT-134while viewing through the microscope. MMP 109 also combines the rasterbeam with the line of sight of the microscope, for example, using a pathfolding mirror 104. The micromanipulator portion of MMP 109 may be usedto adjust (e.g., using a control lever 105) the combining and positionthe raster pattern at a desired exact position on the tissue.

3. Focusing Assembly

A focusing assembly 176 is optionally used for aligning the focusing ofthe laser beam and for aiding in aiming the beam and/or ensuring thebeam is at focus on a treatment plane.

4. Adaptor

An optional adaptor 103 serves to couple the BMS to an OphthalmicMicroscope. In operation the BMS is typically attached to the OM used inthe Operation Room. The OT-134 BMS is attached at the objective side ofOphthalmic Microscope 106.

In an exemplary embodiment of the invention, sub-systems 1-3 areintegrated into one unit 107 (FIG. 3B). Optionally, unit 107 is furtherassembled from two parts, a scanner assembly 108 and a beam combiner109. In an exemplary embodiment of the invention, combiner 109 also hasa micromanipulator functionality allowing for manual repositioning ofthe targeted ablation area without moving the microscope, patient orbeam combiner.

The Scanner:

In an exemplary embodiment of the invention, scanner 102 uses twoperpendicular mirrors in a beam reflecting region 110, each mounted on aDC galvanometer (“galvo”) or other angular actuator. By using twoperpendicular actuators, the laser beam can be scanned by the twoperpendicular mirrors to create variety of shapes, depending, forexample, on the design and setting of the electronics that drives thetwo mirrors. Many suitable electronics are known and the controlleroptionally provides the control and/or power to the galvos, for example,via a cable 153, optionally extending to a power input 113 in a scannerhousing 111. Optionally, the two galvos and mirror are installed in thesame housing 111. Optionally, the articulated arm from a CO₂ laser 100is connected to scanner 102 at a laser entry port 112. Alternatively,other beam scanning mechanisms, such as known in the art, for example,are used.

Optionally, laser port 112 is also used for inputting a visible aimingbeam. In other embodiments, a separate aiming beam is not provided atport 112, optionally as part of a focus control mechanism, describedbelow. In an exemplary embodiment of the invention, the visible aimingbeam is designed to be co-axial and/or overlap with the CO2 laser beam.

In an exemplary embodiment of the invention, the galvo mirrors and theCO2 lens (in other parts of the system) are dichroic elements for thevisible (red, in the range of 625-650 nm) and the CO₂ IR wavelength at10.6 micron.

The diameter of a CO₂ laser beam exiting the articulated arm of a CO₂laser system is typically a few mm, for example, 6-8 mm. For theablation process the beam is optionally focused to a small spot, forexample, less than 100, 200, 300, 400, 500, 600, 700, 900, 3000, micronsin diameter. Optionally, using a small spot allows to better control anddefine the ablation area and/or to change the laser tissue interactiontype and/or to increase the power density and allowing a faster rasterrate for the same energy density required to achieve an ablationthreshold. In an exemplary embodiment of the invention, a small spot isused to reduce the residual thermal damage created by the CO2 laser, forexample, as described below. In an exemplary embodiment of theinvention, focusing lens 101 is used for creating the small spot. Eithera single lens or a set of lenses, or other suitable optical element,such as a diffractive element, or reflective optics may be used.Typically a spot size of 100 to 500 micron can be used. In the depictedembodiment a single lens with 200 mm focal length is used to provide aspot of 300-450 micron in diameter, which may depend, for example on thesource laser parameters, such as beam uniformity, variability andinitial diameter. Other optics may be used to modify the beam size. Itis noted that in some embodiments of the invention the full sized beamis scanned, rather than a focused beam. Also, for other laser typesdifferent spot sizes may be desirable.

CO2 Laser Aiming Beam:

In an exemplary embodiment of the invention, a visible aiming beam isoverlaid on the CO2 beam (or used when the CO2 beam is off) and isscanned with it. This beam can be used to visualize the spatial extentof area to be treated and/or scan path being followed. Optionally, thisbeam projects a pattern which indicates the boundaries of the tissue tobe ablated when the ablation laser is next used. An optional focusingaiming beam is described below. It should be noted that, in someembodiments, the scanner has a relatively wide angular range and theaiming beam is generally shown only while in motion, even though it canbe shown in stationary state. Alternatively, the aiming beam is poweredeven when the ablation beam is not emitted, for example, as soon is thesystem and/or ablation laser is turned on.

The aiming beam used for laterally positioning and monitoring theborders of the scan pattern is the aiming beam coming from a CO2 lasersystem, such as a Lumenis (Yokne'am, Israel) laser system 40C. It iscollinear by design with the CO2 laser beam. Typically a HeNe or a diodelaser are used. In the depicted system the aiming beam comes from a HeNelaser. Optionally, a green wavelength or other visible wavelength isused for the aiming beam.

Focusing Lens and Thermal Damage:

One reason for using focusing lens 101 is to reduce the residual thermaldamage created by the CO2 laser. Thermal damage is caused to tissueswhere the temperature was high enough to cause biological damage such ascoagulation, but not sufficiently high to cause ablation. The tissue israised to this intermediate temperature when the energy absorbed by thetissue is not high enough to create ablation. Even if the power reachingthe tissue is high, there is a possibility that the tissue will reachsuch “intermediate temperate”. For example, this may happen (1) at thetail of the absorption depth of the laser radiation, (2) if there is aleakage of the thermal energy from the elevated temperature tissue toadjacent tissues. Whereas (1) is inherent to the absorption coefficientof the specific laser wavelength in the tissue, (2) is directly relatedto the time available for such “heat leakage” to take place. The longerthe time—the more energy will leak (e.g., through conductance and/orfluid flow). The typical time for thermal energy to leak to thesurrounding tissues is known as “the Thermal Relaxation Time” (TRT).Typical value of TRT may be on the order of 0.5-1.0 msec.

In order to minimize the thermal leakage to other (e.g., adjacent)tissues and cause thermal damage, it is desirable in accordance withsome embodiments of the invention that the process of reaching theablation temperature in the tissues to be removed occurs in a timeduration shorter than the TRT. It is noted, however that if the energydelivered to the tissues to be removed by ablation is not high enough,that tissue will be heated but its temperature will not be raised enoughto reach ablation temperature, and ablation will not take place. In anexemplary embodiment of the invention, this is met by a tradeoff oflaser ablation parameters which allow to deliver enough energy to causeablation, within a time scale that is less than the TRT, or another timeconstant and/or function thereof.

The use of the lens for focusing the CO2 laser beam on the treatedtissue creates high power density (power per unit area) on the ablatedtissue. This means that a high amount of energy may be delivered to thetissue in short time, in contrast to a situation of low power densitywhere only a small amount of energy will be delivered to the tissue atthe same time, and which may not be sufficient for ablation.Alternatively, to deliver enough energy to create ablation, a longexposure time of the tissue to the laser beam will be required todeliver the necessary energy to the tissue, which time may be longerthan the TRT, and which in turn creates thermal energy leakage andthermal damage, as explained. In an exemplary embodiment of theinvention, high power density and short exposure time to the laser beamis a preferred mode in creating ablation. In an exemplary embodiment ofthe invention, this combination is achieved in the LACS by using afocusing lens to create the necessary high power at the focus spot, andthe scanner which rapidly moves the focused laser beam faster than theTRT.

In an exemplary embodiment of the invention, a long focal length lens isused to allow more working space under the objective for the operatorwho operates using the OM. The focal length of the focusing lens in thedepicted system is 200 mm, equal to the typical focal length of theobjective of typical OM's.

If the system does not operate at the correct focusing distance, thespot size of the focused beam becomes larger, power density is reducedand the risk of causing thermal damage (with or without ablation) may beincreased. In addition, control of the scan dimensions may become lessprecise.

The Focusing System:

In an exemplary embodiment of the invention, longitudinal aiming forpositioning the CO2 laser focus onto the plane of the tissue beingtreated is performed using a twin diode laser aiming technique. Thebeams from two visible diode lasers 130, (e.g. a wavelength ofapproximately 650 nm) are directed to converge to a single spot at thefocal plane of CO2 laser focusing lens 101. Optionally, the output powerof each of these diode lasers is in the range of 25 μW to 200 μW.Preferably the range is between 40 to 100 microwatt. In the depictedsystem the power of each laser diode is 50 microwatt. Optionally, thelaser power is selected to avoid retinal or other ocular damage thereby.

In an exemplary embodiment of the invention, the lasers are focused, forexample, each provided with a lens of focal length of 200 mm.Optionally, this causes defocusing at the retina, thereby reducingpotential damage. Optionally or alternatively, this focusing increasestheir accuracy of use.

Optionally, the two separate aiming beams are never simultaneouslydirected at the same tissue point (e.g., a separation is optionallydefined for when they are at a correct focal distance), but even if sucha situation would occur the maximum total power would be less than 0.55mW, still within the limit of Class II system. Alternatively, when thebeams overlap, that is the correct focus. Optionally, the system isconfigured so that up to about 0.5 mm separation of the aiming laserlight points, the focus is substantially acceptable.

In an exemplary embodiment of the invention, tiny alignment screws(e.g., 2 for each diode laser) allow the precise alignment of the laserssuch that the two diode lasers overlap at 200 mm.

A potential advantage of such a aiming method over systems where theaiming beam is directed through the cornea such as photo-coagulators orSelective Laser Terbaculoplasty (SLT) systems, is that unlike the lattersystems, in the twin beam aiming method the aiming beams can be directedtowards the sclera and not through the cornea or onto the retina soexcessive retinal exposure can not occur. Optionally or alternatively,the focusing is shown at the location of the desired focus, the uppersurface of the sclera. While, optionally the focus aiming beams do notmove, optionally they may be scanned with the scanner.

A potential advantage of such an aiming system lies in a way in whichsurgeons often use an OM in the OR (operating room). The surgeons oftenchange the focusing setting and the zoom stetting during operation. Itis very common that a surgeon will use different focusing distances ashe maneuvers with the focus and zoom options of the OM. This is may be,at least in part because the eye optical alignment is not fullyrepeatable, even in normal eyes. Such deviation from time to time willcause the BMS to move out of its focus, even after it has been alignedonce. It is therefore a potential advantage to have a simple method tomonitor the focusing. Below is described a mechanism for correcting thefocal length. An additional potential advantage is that a focusingelement can be replaced to an element with a different focus and also adifferent matched set of focus aimer. Optionally, such a combination oflens and focusing beams is provided as a single unit.

In an exemplary embodiment of the invention, the BMS is mounted onapportion of the microscope which does not move with focus, zoom and/orlens changes of the OM and additional focal adjustment of the laser beammay be avoided after an initial focusing (e.g., absent patient motion).

In an exemplary embodiment of the invention, any necessary correction isapplied by moving the scanner and its optics (which consists of thefocusing lens of the CO2 laser and the two focusing diode lasers)relative to the MMP using a linear displacer, for example, a screwmechanism.

In the depicted system the screw mechanism is realized using amicrometer 115.

Optionally, the two optical systems, that of the OM and that of the BMS,should have overlapping focuses within the “depth of field” (DOF) of theBMS optics. DOF is defined as the axial distance along the optical axisof an optical system in which the focal spot size has not changedappreciably.

Typically, the DOF is related to the wavelength of the beam, the focallength of the condensing optics, and the diameter of the beam. The DOFmay also relate to how tight the design is, in terms of toleratingcertain changes in the spot size at the focal plane and still notjeopardize the essential performance characteristics of the opticalsystem.

According to these guidelines, the DOF in the depicted system is in therange of +/−4 mm.

Taking into account the distance between the focusing diode lasers inthe depicted system (39 mm) which are at the two sides of the ablationlaser focusing lens, the focal length of the focusing lens which is 200mm, and the depth of field which is +/−4 mm, the distance between thediode lasers focused spots of the Focusing System at the treatment areacan be 780 micron apart (pre convergence or post convergence) at thetreated tissue and still be within the DOF of the BMS.

In most ophthalmic microscopes (OM) the objective has a focal length of200 mm. Optionally, the two optical systems, the one of the OM and theone of the depicted system, have the same focal lengths. If the operatorobserves that the spots of the two diodes coming from the focusingassembly do not overlap and are separated by more than the alloweddistance as defined by the DOF, the operator can finely adjust theposition of the CO₂ laser focusing lens using micrometer 115. Thisadjustment mechanism may also be used if the focal distances of the twooptical systems (OM and BMS) are not the same.

A cross-sectional view of the ablation system is shown in FIG. 4A. Anisometric view of BMS 174 is shown in FIG. 4B.

The Path Folding Mirror of the Beam Combiner:

The beam exiting the scanner and the focusing lens can be oriented tothe desired direction using a path folding mirror 104 which is part ofthe MMP. The folding mirror is optionally connected to levers (e.g.,105) which can adjust the position and/or orientation of mirror 104, andthereby the exact position of the scan pattern on the treated tissue. Insome embodiments the exact positioning of the scan pattern is crucial tothe procedure, as ablation must take place in the desired location.Optionally, the manipulation is manual. Alternatively, one or moremicromotors are provided and manipulation is remote, manually orautomatically, for example using a computer. Optionally oralternatively, a remote and/or automatic manipulation system is providedfor screw 115.

The Micromanipulator:

In an exemplary embodiment of the invention, the MMP has five screws forattachment onto the adaptor, in particular to a flange of a ring of theadaptor (542, FIG. 4B). Optionally, ring 542 is not a complete ringand/or does not overlap axially with the path folding mirror. In oneembodiment, the ring is complete and does not reach down to the axialposition of the mirror. Optionally, two sets of screws are provided, forattachment of the MMP in one position or in a flipped position.

This configuration allows safe attachment onto the adaptor and/or safe(e.g., without danger of disconnection) rotation of the BMS around theaxis of the OM objective. As an example of such configuration, twoscrews 120 are fixed (e.g., glued). One screw 121 is used to completethe attachment of the BMS onto the adaptor, for example, by defining atriangle of points which define a diameter that is smaller than an outerdiameter of the flange, for example, fitting in a groove ordepression(s) thereof. Screw 121 is partially locked to the extent thatit does not allow the BMS to be removed intentionally orun-intentionally (e.g. dropped by mistake). In this position, whenscrews 4 and 5 (122) are open, the user can rotate the BMS and bring itto the desired rotational position without risk of dropping; and whenthe BMS is at its desired rotational position screw 4 and/or 5 (122) arelocked preventing incidental movement or rotation. Optionally, one ormore screws is loosened a bit (and retightened) at a later time, toallow rotation of the BMS around the axis of the OM. In an alternativeembodiment, two screws are maintained in a tight configuration and onlyone screw is loosened to allow rotation.

In an exemplary embodiment of the invention, the MMP has an opening 123which is large enough so that when the BMS is attached to the adaptorand OM the operator can view freely through opening 123, except,possibly, for partial blockage at the beam combining mirror.

Optionally, opening 123 has a diameter typical to the diameter of the OMobjective. In the depicted system the opening diameter is 45-50 mm indiameter. As shown, path folding mirror 104 is optionally mounted at theedge of opening 123.

In an exemplary embodiment of the invention, folding mirror 104 is wideenough (e.g., twice or more the width of the scanned laser beam, toreflect both the CO2 laser beam coming out of CO2 laser beam focusinglens 101 and the two laser diode 130 beams used for the focusing system.The width of the active area of the folding mirror may depend on wherethe mirror is positioned along the optical axis of the system. In anexemplary embodiment of the invention, the active area has a widthbetween 20 and 70 mm. Optionally, the active area width in the range of30 to 60 mm. Possibly the width is between 35 and 50 mm. In the depictedsystem the width of the path folding mirror is 39 mm.

In an exemplary embodiment of the invention, the folding mirror iscoated with dichroic coating having high reflection in its active areaboth in the infrared (or other) range for the CO2 (or other) laser beamand the red range (˜625-650 nm) for the aiming beams (or otherwavelength, according to the color of the aiming beam). In an exemplaryembodiment of the invention, the folding mirror can be coated in bothsides. For example, this allows higher flexibility in configuring theBMS in all OR's: in right and left configurations, and back and frontconfigurations.

In the depicted system described the folding mirror is mounted at theside of the beam entrance to opening 123. A potential advantage of thisdesign is that the operator gains extra free working distance which isin the order of the MMP opening, as compared to a design where themirror and its manipulators are distanced from the scanner and focusingoptics. This extra working space may be needed for the operator to moreeasily operate and to reduce the risk of incidental touchingunsterilized parts of the BMS.

Adaptor:

Adaptor 103 is a mechanical part used to attach BMS 174 onto theophthalmic microscope (OM). In an exemplary embodiment of the invention,adaptor 103 is connected to the OM using a standard means, such as withscrews and an interference fit of a tongue 180 in a matching groove inthe OM, to the bottom of the OM near its the objective. Typically,threaded holes in the OM are factory prepared by the manufacturer of theOM specifically for attaching accessories to the bottom of the OM. Sincedifferent OM have different holes and threads for connecting theadaptors, different adaptors are optionally provided for different OM's.After the adaptor is attached to the OM, the micromanipulator is hookedonto the adaptor, for example, as described above. Optionally, adaptor103 too has a round aperture 133 to allow the operator to freely lookthrough and use the OM.

Scanner Control Unit

In an exemplary embodiment of the invention, the galvanometers aredriven by electronic signals which create the desired patterns. The usercan select the scan pattern (e.g. square, rectangular, arc) the exactdimensions of the pattern (e.g., with resolution of 0.2 mm), and thescan parameters (e.g. scan speed and raster line overlap). This is doneby the controller (not shown). It should be noted that for somepatterns, all of the scanning and ablation is on one side of eh cornea.In others, such as a arc of greater than 180 degrees, the BMS may berotated to allow ablations of the different parts or a scanning isperformed in a pattern which avoids the cornea and/or the laser isturned off or blocked while the scanning overlies the cornea.

The OT-134 in the Operation Room:

In an exemplary embodiment of the invention, the LACS is attached to theOM in the OR using adaptor 103. It is also connected to the CO2 lasersystem through CO2 input port 112.

In some ORs the setting of the OR will prevent the positioning of theLaser system at the desired location for conveniently attaching the BMSto the CO2 laser system. In an exemplary embodiment of the invention,for example to increase the flexibility of configuring the BMS in the ORthe, the BMS can be assembled in variety of configurations. In anexemplary embodiment of the invention, the BMS can be used with the CO2laser system at its right, or left positions, at the front or at theback side of the operator.

FIGS. 6A-6D show various arrangements of controls on BMS 174. In anexemplary embodiment of the invention, manipulation lever 105, forexample, can be connected to either a port 182 or a port 184. Similarly,micrometer 115 is optionally disconnected and reconnected at a desiredside. Alternatively, scanner 102 with micrometer 115 is detached fromadapter 103 and/or MMP (e.g., by opening screws 135) and then flippedand reconnected. Optionally or alternatively, MMP can be flipped andattached in mirror manners to an adaptor. This may require differentplacement of the screws in the MMP and/or a longer flange on theadaptor.

It should be noted that FIGS. 6B and 6D show adapter 103 not coupled toBMS 174.

A LACS can be designed with other modular components that can beattached to each other in various configurations according togeometrical needs. Optionally or alternatively, such modular componentscan be replaced according to need, for example, an adapter changed tomatch an OM objective design or a focusing assembly replaced to match adesired focal length, a scanner replaced to match a desired range ofmovements or a MMP (or only a mirror portion thereof) replaced to matcha microscope field of view size and/or wavelength of various aimingbeams that are used of aiming. In an exemplary embodiment of theinvention, the parts that are modular are designed to be disconnectedand reconnected with a minimum of work and without substantiallyaffecting alignment, for example, only requiring opening and closing offewer than 5 screws and/or having interlocking and/or matching surfaceswhich ensure a known alignment of optical elements. Optionally oralternatively, some simple calibration tools are provided, for example,the manual micromanipulation and focus control.

Scan Patterns:

The scanner can create various scan patterns. For example, such patternscan include:

Square, rectangular, Sectored disc (700, FIG. 7A) and concave shapes.

The sectored disc (SD) is a curved pattern, that follows the eyecurvature of the cornea, iris or limbus, for example. The SD is definedby the two Diameters of the inner (ID, 702) and outer (OD, 704) circlesof which the disk is a sector, and the width 706 of the sector, whichmay also be seen as an angle ! (708). The scan pattern border need nothave exact arcs of a circle and may have other shapes, like an arc of anellipse or a free-form curve.

Various scan paths may be used within the pattern. One example is an x-yraster. FIG. 7B shows a scan path 710 where the scanning is in curvedlines, optionally parallel to the curvatures of the scan shape. FIG. 7Cshows a scan path 712 with the scanning direction perpendicular to thecurves. Optionally, overlap between spots in uniform in scan path 710,and non-uniform in scan path 712.

FIG. 7C shows a scan shape 714 with a limbus conforming curved concaveborder 718 and a straight or otherwise non-parallel distal border 716.

In an exemplary embodiment of the invention, the SD can be programmed tocreate discs with ID and OD in the range: 4.0 mm (or 8 mm)<ID<15.0 mm,OD<17.0 mm (or 20 mm), which cover the range of typical human eyes.Other sizes, smaller or larger may be used as well. Width is, forexample, between 1.0 and 7.0 mm, optionally between 1.0 and 5.0 mm. Inthe depicted system, width is between 1.0 and 4.0 mm.

In an exemplary embodiment of the invention, it is noted that whenablating large areas, a rectangle is a poor approximation of the scleralarea above the Schlemm's canal and this may lead to greater danger ofperforation. Optionally, a plurality (e.g., 2-5) of smaller (e.g., 0.7-2mm in length) areas are individually ablated. Optionally oralternatively, a curved form is used to match the shape of thelimbus/cornea.

Enforced Delay

In an exemplary embodiment of the invention, the computer control systemdoes not act on an ablation command if a repeat delay time did not passsince the last ablation. Optionally, this delay is a parameter, forexample, provided on a memory card. In an exemplary embodiment of theinvention, the delay is selected so as to be long enough to allowclinically useful percolation to be identified in an ablation area.Optionally, the delay is not so long as to allow non-clinically usefulpercolation to be mistaken for clinically useful percolation.Optionally, the delay is between 1 and 15 seconds, for example between 1and 3 seconds.

Exemplary Methodology of Identifying the SC Position:

The inventors have discovered that if the anterior perimeter line of thescan pattern is positioned over the limbus, after the flap was created,the SC (Schlemm canal) is repeatedly exposed if the width of the scanpattern is 1.4 mm, e.g., along the direction which extends away from thecornea and limbus. In an exemplary embodiment of the invention, thisconsideration is applied to any treatment of the Schlemm canal for anytype of non-penetrating filtration surgery (e.g., other lasers, manualor automatic) are aimed for such a region. Optionally or alternatively,such surgery is carried out in two steps. A first step where the entiresuspected area is ablated to a certain depth, for example, a fixed depthor until the Schlemm canal (SC) becomes visible, e.g., based on thebeginning of percolation thereof (e.g., percolation that takes severalseconds to cover the surface). Optionally, when the SC is exposed thewidth of the ablation area is reduced to, for example, between 0.8 and1.2, for example, 1 mm overlying the SC. Optionally, the length (e.g.,along the curvature of the limbus) is also reduced at this time, forexample, to 1-2 mm.

Optionally or alternatively, the scanning is performed in small subregions (e.g., 2, 3, 4 or more), for example, 1-2 mm in length (aroundthe circumference of the eye). In each such region, the SC may bedetected separately and/or ablation be carried out to different depths.

Although the typical width of SC is approximately 350 micron, it may beadvantageous to create a narrower or wider percolation zone (e.g., 0.2,0.3, 0.4, 0.5, 0.7, 1, 1.5, 2 mm, or intermediate or greater width) suchthat percolation can take place from the SC and its neighborhood zone.Optionally or alternatively, a separate reservoir is created, or thezone is made wide enough to reduce adhesions between the flap and thepercolation zone.

Eye Protector:

In order to prevent incidental irradiation of the CO2 laser beam, theoperator optionally uses an eye protector, which covers the cornea andis made of material that absorbs or reflects CO2 radiation, therebysubstantially attenuating and/or completely blocking undesired radiationfrom reaching sensitive parts of the eye which are not supposed to beirradiated.

An example for such eye protector is a contact lens which may constitutewater in a concentration of above 40% or above 50%. In an exemplaryembodiment of the invention, the high concentration of water improvesthe blocking properties of the eye protector. Optionally, the protectoris a section of a sphere or is a curved rectangular element, and isoptionally sized to fit an adult eye. The protector is optionally heldin place by a temporary adhesive. Optionally, the lens has a thicknessof less than 3 mm, less than 2 mm or less than 1 mm. Optionally oralternatively, the lens is placed over the pulled back flap andoptionally includes a depression therein to receive the flap.

Optionally, further blocking properties may be achieved if the eyeprotector has selective transmission properties, by which the aimingbeams that emit at the red parts of the spectrum are blocked by the eyeprotector as well as the CO2 laser in the Infrared. Optionally, howeverthe eye protector is transparent enough to allow the operator to viewthe inner part of the eye during operation. This transparency may assistin monitoring the status of the eye during operation.

Such selective transmission can be realized by doping the eye protectorwhich is otherwise transparent to the visible light (such as contactlens) with a dye (blue, purple) that selectively absorbs the red aimingbeams.

In an exemplary embodiment of the invention, the protector includes anaperture (e.g., on the order of the size of the ablated area, or twicethe size in one or two dimensions, optionally, not over the cornea,optionally having a curved shape following the cornea) for the CO2radiation to path through and/or includes a section with lowerreflection or absorption, for example, having a reduced water contentand/or thickness.

Exemplary Surgical Procedures

FIG. 8 is a flowchart of a general procedure 800 for eye treatment, inaccordance with an exemplary embodiment of the invention. After a briefdescription, a detailed description of exemplary procedures will beprovided.

At 802, various laser and scan parameters are optionally set orselected. At 804, a flap is cut in the scleral tissue overlying theSchlemm canal. The order of the two acts may be changed, as can be theorder of other of the acts decided below. At 806 the laser beamoperational field is positioned at a correct location on the eye (e.g.,1.4 mm over the Schlemm canal). At 808, an eye protector is optionallyprovided on the eye, with a window exposing the treatment area. At 810 afirst ablation is carried out until the Schlemm canal is nearly exposedand percolation starts. At 812, further ablation is more limited toareas above and adjacent the Schlemm canal. At 814, the ablation areamay be washed between ablation acts. At 816, the ablation is completedand a topical treatment, such as anti-inflammatory or other bioactivematerial or a spacer may be provided at the ablation area. At 818, theflap is closed, optionally, with one or two sutures at either end of theexposed Schlemm canal. At 810, topical medication may be provided afterthe procedure, for example, for several days and weeks. Optionally oralternatively, systemic medication may be provided or IOP-reducingmedication may be provided. At 822, a needling procedure, where a smallobject is placed in the ablated region and optionally moved around toseparate and/or reduce adhesions between the flap and sclera, may beapplied. Optionally or alternatively, the eye may be punctured to reducepressure. It should be noted that such needling and/or puncturing areoptionally applied after the procedure is completed and possible thetissue healed, for example, to combat adhesions and/or other causes ofreduced percolations. Such times may be, for example, several weeks ormonths or years and are optionally performed in response to a measuredincreased IOP.

Exemplary Specific Procedure and Aftermath

Typically, surgeries are performed in the ophthalmic surgery room, underlocal anesthesia (e.g., retrobulbar, peribulbar, sub-tenon, or topical),unless there is an indication for general anesthesia.

1. Following routine preparation of the eye for sterile surgicalconditions a speculum is placed.

2. A fornix-based peritomy is performed at the superior limbus, and theTenon's capsule is also dissected, to expose the sclera. The location ofthe flap is optionally under the upper eyelid.

3. Optionally, careful hemostasis is performed using cautery.

4. A partial thickness (e.g., approximately one half) limbal-basedscleral flap is dissected at the limbus into clear cornea. The length ofthe flap is, for example, between 2 and 6 mm. Optionally, the length ofthe flap is between 4 and 6 mm. The length of the flap is, for example,between 2 to 6 mm. Optionally, the length of the flap is between 3 and 5mm. Optionally, the length of the flap is approximately 4 mm.

5. The desired shape for the scanning area is set. Optionally, the shapeof the scan pattern is rectangular or square or that of a sectored discor arc.

6. The appropriate scan area size is set.

7. Laser beam focusing is carried out.

8. The treated area on the patient is defined.

9. The laser power is optionally verified. In an exemplary embodiment ofthe invention, the laser power at the laser entrance port of the BeamManipulating System is between 18 to 30 watts. Optionally, this power isbetween 20 and 26 watts. Optionally, the power is between 22 to 24watts.

10. Laser mode is verified. Optionally, the laser mode will-beContinuous.

11. Optionally, The focus of the laser beam on the targeted area isverified using the BMS focusing assembly.

12. The cornea is protected against an incidental irradiation by the CO2laser. Such protection can be made by way of example using soft contactlens which absorbs the CO2 radiation. Optionally, this contact lenscontains more than 50% water. Optionally or alternatively, the Cornea isprotected against incidental radiation of the visible aiming beam(s). Byway of example, same eye protector can protect against visible light andagainst infrared radiation. Optionally, the eye protector is made ofcontact lens material and is tinted with color to substantiallyattenuate the visible radiation.

13. The treated area is verified by observing the pattern of the redHeNe laser aiming beam of the CO₂ system.

14. The laser is switched to READY. The surgeon verifies that the laserREADY light indication illuminates.

15. A footswitch may be pressed to activate the ablation. Optionally,the scanning is continuous and optionally synchronized with the laser(optionally by synchronization with the laser shutter) so that wheneverthe laser is turned on, it is scanned according to the pattern withoutneed for communication between the controller and the laser source.Optionally, such communication is used. The first ablation scanning(step) is verified to be done properly.

16. The HeNe aiming beam indicates the ablation area. The dimensions ofthe indicated ablation area should include the Schlemm's canal area. Ifrectangular or square or arc patterns are used, the 2 anterior red dotsof the aiming beam or the anterior line (e.g., dots added at theanterior two corners of the ablation region, which assist in alignmentthereof with the limbus) are optionally placed on the limbus line priorto first ablation. Optionally, the ablation pattern length is between 1and 5 mm. Optionally, the length of the scan dimension is between 2 and4 mm. Optionally, the length of the scan dimension is between 2.5 and3.5 mm. The width is, optionally, 1 to 3 mm long. Optionally, 1 to 2 mm.Further optionally, 1.2 to 1.8 mm. If a sectored disc is used theconcave edge of the pattern is overlaid on the limbus.

17. Wait at least 1-2 seconds between consecutive ablations. Optionally,the ablation is also used to seal any blood vessels that leak, forexample, as an automatic consequence of the scanning. Alternatively, thelaser is separately used for such sealing. Optionally the system isdesigned (e.g., as described above) to electronically prevent therepeated ablation within a time period of, for example, less than 1-2seconds (repeat delay), thereby ensuring that the percolation can takeplace and the physician and/or a computerized imaging system had time todetect percolation, if any. In many cases, it appears that ifsignificant percolation does not appear within 2 seconds, suchpercolation does not appear.

18. Performing repeated ablations until the outer wall of the Schlemm'sCanal is ablated. In an exemplary embodiment of the invention, the laserparameters are selected to minimize thermal damage to the bottom of theablated area, through which percolation is expected.

19. The surgeon may work separately on the scleral bed formation withthe laser and on the percolation zone above the Schlemm's canal area.The scleral bed size is optionally about 4×3 mm².

20. The charred tissue is optionally wiped with a wet sponge every 1-3laser scans. Alternatively, a spray may be used

21. Optionally, the laser parameters are modified as required within therecommended working parameters detailed in the above, for example,responsive to rate of ablation or amount of fluid or thermal damageobserved.

Operating the OT-134 system is optionally continued until sufficientpercolation is achieved. While the laser procedure is stopped when thesurgeon decides that sufficient percolation is achieved, it isrecommended in some cases that the total length of the percolation zoneis at least 3 mm long and at least 0.5-1 mm wide.

22. The scleral flap is optionally repositioned and secured in placeusing 2 interrupted 10-0 nylon sutures.

23. Healon 5 high molecular weight Ophthalmic Viscosurgical device(viscoelastic substance) is optionally applied beneath the repositionedflap. Other spacers and/or spacer materials may be used here.

24. The conjunctiva is optionally repositioned and secured in placeusing interrupted 10-0 nylon sutures.

25. Antibiotic and steroid ointment are applied and the eye isoptionally closed with a patch and a shield. Optionally, the use ofanti-metabolite drugs (such as Mitomycin C and 5-FU), and/or spacers(such as the STARR Collagen drainage device, e.g., degradable orpermanent) is optional, e.g., per physician discretion. The use ofparacentesis and/or an anterior chamber maintainer is optionally left tothe physician's discretion.

Exemplary Post Surgical Management

1. Post-operatively the patient is optionally treated with topicalcorticosteroids (e.g., Pred Forte drops) at least every 3 hours duringwaking hours for one week, and then every 6 hours during waking hoursfor additional 5 weeks. At the end of the steroid treatment, it is inthe physician's discretion to stop or to taper off the steroidtreatment.

2. Optionally, after 2-4 weeks of steroids, NSAIDS treatment isinitiated; Optionally, Voltaren Ofta is administered.

3. One week or more postoperative, if the physician believes, at his/herdiscretion, that the post index IOP is too high for the patient, thesteroid treatment is optionally stopped and NSAIDS treatment (e.g.,Voltaren Ofta), is begun. If IOP is reduced to an acceptable level, thecorticosteroids treatment is optionally resumed.

4. When NSAIDS treatment is initiated, this treatment is optionallyadministered for 8 weeks.

5. Post-operatively, topical antibiotic treatment such as 4th generationfluoroquinolone (e.g. Vigamox), is optionally administered, for example,4 times daily, for 2 weeks.

In an exemplary embodiment of the invention, the usage of gonio-lens isavoided in the first 3 weeks post procedure unless IOP increases tovalues >18 mmHg. If performed, a 4 mirror gonio-lens is optionally used.

1. Goniopuncture is an optional measure to reduce the IOP. This measureis also optionally preserved for cases that failed to respond to theother measures described above. The decision to perform the procedureand its timing is by physician discretion and is typically several days,weeks or months after the laser ablation procedure.

2. Needling (separating the flap from underlying scleral tissue using aneedle that is inserted between them and moved) is another optionalmeasure to reduce the IOP and/or adhesions. The decision to perform theprocedure and its timing is by physician's discretion and is typicallyafter healing is complete or nearly complete, for example, to combatadhesions.

3. Anti-glaucoma medications may be used at a physician's discretion.

4. Using anti-metabolites during needling is at a physician'sdiscretion.

Notes:

1. In an exemplary embodiment of the invention, the flap length isselected to be between 4 to 6 mm, as, with a broad flap one can create abroad percolation zone, which in turn may be more effective in relievingthe intro-ocular pressure than a narrow flap. Optionally, the ablationarea encircles at least 10, 20, 30, 60, 90, 180 or more or intermediatedegrees of a circumference of the cornea.

2. Optionally, for example, because the sclera has inherentin-homogeneities, it may be useful to perform consecutive ablations ofsmaller areas than to perform a full length ablation throughout the flaplength. Optionally, each such small area is 2 to 3 mm's long, within aflap length which is 5-6 mm long.

3. Optionally, the ablation is performed above (and optionally along)the Schlemm's Canal (SC), which is the region where percolation takesplace in normal people.

Typically, the SC is covered by scleral tissue, and its position cannotbe indentified precisely a-priori. Optionally, the following method isused to determine its location: The flap is raised, and the limbus isexposed after the formation of the flap. It may be useful to identifythe limbus after flap formation because the position of the flap isoften not the same along the thickness of the sclera.

Alternative System (OT-133)

FIG. 9 shows an alternative system 900 for laser ablation control, whichwas evaluated in preclinical and in clinical trials.

In this system, a path folding beam combining mirror 902 is placedopposite of an output of a beam scanner 102. A focusing system 904includes a lens 906, for example, as described above. Manipulation ofmirror 902 is via a micromanipulator 908, for example using a knob 910,mounted on an opposite side of an aperture 912 from scanner 102.Aperture 912 is optionally aligned with a field of view of an OM (notshown). In an exemplary embodiment of the invention, the scanned beam914 has a width of, for example, 0.3 mm when it impinges on an eye 916.Optionally, a distance 918 between system 900 and the eye is shorter(e.g., 100-120 mm), for a same lens 906, as compared to the OT-134,described above.

Evaluation, in a pre-clinical phase (Reference—Assia E I et al) includedthree experimental models: enucleated sheep and cow eyes (n=18) todetermine optimal irradiation parameters, live rabbit eyes (n=20) totest feasibility and cadaver eyes (40 procedures in 20 eyes) to studyeffects in human eyes tissue. After a half-thickness scleral flap wascreated, deep sclerectomy was performed by CO2 laser applications on thescleral bed down to the trabeculo-Descemet's membrane.

Results: Fluid percolation was repeatedly achieved without penetrationin sheep and cow eyes using scanned laser energy of 5-10 W at a pulseduration of 200 microsec and a working distance of 25 cm. In liverabbits, deep sclerectomy was achieved without perforation in 19/20eyes. Intraocular pressure was significantly decreased on the firstpostoperative day (10.3+/−5.1 mmHg lower, on average, than in thenon-operated fellow eye; P<0.001), and this persisted for 21 days.Operations on all cadaver eyes resulted in effective fluid percolation.Penetration of the scleral wall occurred in five cases only afterrepeated laser applications with high energy. Histologically, a thinsclerocomeal intact wall was demonstrated at the sclerectomy bed.Collateral tissue damage did not extend beyond 100 micron, and adjacentstructures remained unharmed. This preclinical phase shows that CO2laser-assisted deep sclerectomy is a feasible and apparently safeprocedure.

The clinical phase included an evaluation of safety and short termperformance on 23 glaucoma patients in multi national multi centraltrial. All patients had POAG or PEXFG.

The results:

Fluid percolation was achieved in all cases

No significant complications related to the laser treatment wereobserved

The anterior chambers were deep and stable in all case, even when theIOP was low.

On day 1 all of the cases, except one with acute inflammatory reactionsecondary to an intra-operative event, had IOP lower than 12. In 16 outof the 20 cases the IOP was 7 mmHg or lower.

The results indicated that achieving the surgical goal (fluidpercolation) and short-term effect (low IOP after surgery) is feasibleand practical using the OT-133 system.

The success rate of the 23 patients:

The system demonstrated safety and short term efficacy.

5 patients dropped out due to mistakes in the procedure (e.g., andconverted to trabeculectomy) and protocol deviations

Success criteria defined as IOP under 22 mmHg.

The success rate at 6 months was 76.4% (see also FIG. 10).

OT-134 Testing

The OT-134 was tested in a similar dual phase way: Pre-clinical andclinical studies.

The objective of pre-clinical study was to verify the safety of theimproved device (OT-134) when used for scleral tissue ablation withpossibly more optimal combinations of laser power level, scanner dwelltime and overlap values within a specified range of parameters.

The pre-clinical phase included three experimental models: enucleatedpig eyes (n=60), live rabbit eyes (n=24) and human cadaver eyes (40procedures in 20 eyes) to study effects in human eyes tissue.

The enucleated pigs' eyes were used to determine possible scleral flapand scanning area dimensions. The objective was to determine thescanning area dimensions that will reveal the Schlemm's canal whileavoiding ciliary body damage. Four flap widths were examined: 3, 4, 5,and 6 mm.

The trial on human cadaver eyes also used to determine the dimension ofthe flap size (3, 4, 5, and 6 mm width) and the scanning area width ofeach laser application was up to 90% of the flaps' width (optionallybetween 40% to 60% of the width) and the scanning (anterior-posterior)area of each laser application was 5 sqr mm to 20 sqr mm possibly up to1.4 mm from the posterior limbus line. In some embodiments of theinvention, the scanned area is between 2 and 20 sqr mm, for example,between 2 and 10 sqr mm. The anterior two aiming beam are laid on theposterior margin of the limbus, and a length of 1.4 mm of the scanningarea—revealed as containing the Schlemm canal were ablated, possiblyenabling the physician to expose the canal in a simple, safe and easymanner. Laser treatment in that area gradually ablated the superficialscleral layers one by one revealing the Schlemm's canal. Once Schlemm'scanal was recognized, the scanned area dimensions were graduallyreduced. This shows that two stage ablation, with different ablationareas, can be used.

In the next stage the system was tested (for safety) on a group of 12rabbits (24 eyes) divided into 4 subgroups, according to follow-upduration until sacrifice (4 rabbits were sacrificed immediatelyfollowing procedure (upon recovery), 3 were sacrificed 10 and 15 daysafter procedure, respectively and 2 were sacrificed 21 days postprocedure). Both eyes were operated on in each rabbit. Recommended rangeof laser and scanner parameters were used in all procedures (Laser powerrange of 20 W to 26 W was used; Scanner dwell time was set to 100 to 400μsec, and 10% to 40% beam overlap of diameter in all cases). Variousshapes and dimensions of scleral ablation area were examined (e.g.,rectangle, slotted disc).

Results: Twenty-four eyes of 12 New Zealand White rabbits were operatedon. Laser power was 24 W in 20 procedures, 22 W in 2 procedures, 20 W in1 eye and 26 W in 1 eye. Percolation was repeatedly achieved, except forone eye, in which laser application was too posterior from the limbus.In 1 eye (#2699 left eye, group 1.1) an inadvertent ocular penetrationwas done with the crescent knife during flap creation, and therefore nottreated with laser. Micro-penetration of the scleral wall occurred in 4(17.4%) eyes.

These experiments showed that the learning curve is short and theprocedure can be generally safe and simple. Optionally, there are nospecial requirements for the OR (e.g., the same needs as for cataractand/or trabeculectomy).

The procedure is safe and simple.

During the post operation recovery period, the interface between theablated sclera and the flap was filled with blood and plasma. In eyesexamined immediately post-operation, inflammatory cells were observed.Ten days post operatively, the crater was filled with connective tissue.Thermally damaged tissue shrunk in size. Thermally damaged tissue almostdisappeared. Twenty days after the procedure, trabecular meshwork(encircled) underneath the scar did not show any signs of thermaldamage.

Thermal Damage

In some experiments with the OT-133 failure was associated with PASformation. PAS formation can possibly be attributed to thermal damage.Heat generated during the tissue ablation possibly causes localinflammatory reaction leading to tissue adhesions and scarring. In anexemplary embodiment of the invention, decreasing and controlling localtissue inflammation improves the long-term results of the CO₂ laserfiltration procedure.

In all examined eyes, certain thermal damage was seen on lateral wall ofablation crater following the procedure. However, it was found that forsome operating parameters, substantially no thermal damage was presentin the floor of the crater, made up of loose trabecular meshwork, wherepercolation takes place.

Histological studies demonstrated a deep crater in the scleral wall downto the trabeculo-Descemet membrane, with no perforation. Neighboringstructures, including the iris root, ciliary body, adjacent sclera andcornea, were not affected and remained undamaged. No inflammatory cellswere present 10, 15 and 20 days following the procedure and nosignificant differences were noted in tissue response 10, 15 or 20 daysafter the procedure. Thermal tissue damage up to 200μ could be detectedmerely at the lateral walls of the ablated sclera. Thetrabeculo-descemet membrane was free of thermal damage.

This is illustrated in FIG. 11C, where a thickness of thermally damagedtissue 1114 at the sides of a carter 1112 in scleral tissue 1110 isgreater than damaged tissue 1116 at a bottom 1118 of the crater. Thecrater is the vacant space in the sclera above the Schlemm's Canal (SC)created by the removal of the sclera by ablation, the bottom being theintact thin layer above the SC.

FIGS. 11A and 11B illustrate reduced thermal damage for some parametersover others for non-percolating tissue. FIG. 11A shows a histology oftissue ablated using 18 watt, dwell time 500 microseconds and overlap of20% (using OT-133). The thickness of thermally damaged tissue is about250 microns. FIG. 11B shows a histology of tissue ablated using 24 watt,dwell time 220 microseconds and overlap of 20% (using OT-134). Thethickness of thermally damaged tissue is about 150 microns.

The parameters of the scanning were selected based on very extensivepre-clinical trials on pig eyes, alive rabbit eyes and cadaver humaneyes. Generally, ideal parameters for the procedures with the OT-134were found to be energy of 24 watt, dwell time of 200-300 μsec, (e.g.,300 microseconds) and overlap of 30%.

The experimentation also showed potential advantages of using the OT-134with the determined and control focus, stability and correct parametersof working results in reducing thermal damage to the tissue asdemonstrated by the Comparison of scleral thermal damage depth atdifferent operating parameters (e.g., FIGS. 11A and 11B).

The clinical phase of the OT-134 device was preformed as amulti-centered, multi-national clinical trial, performed at 3 sites:

-   -   14 laser assisted non-penetrating deep sclerectomy procedures,        preformed at the APEC hospital, Mexico-city, Mexico.    -   Thirteen subjects were treated at the Siloam Eye Hospital,        Madanapalle, India.    -   Ten subjects were operated at the East-Sight Recover Center in        Moscow, Russia.

Results are described below.

Overlap

FIG. 12 illustrates overlap between spots, in accordance with exemplaryembodiments of the invention. A plurality of laser spots 1200 overlap(e.g., as measured by distance between beam centers as compared to beamdiameter), at overlaps 1206 between spots in a row 1202, overlap regions1204 between rows 1202 and multiple overlap regions 1210 and 1208.

In an exemplary embodiment of the invention, the laser scanning isdiscrete, e.g., with a spot moving time shorter than 20%, 10% of thespot dwell time. In this case, overlap is defined between adjacent spotsin row and between rows. If the scanning is continuous, overlap ismainly meaningful between rows. As noted above, overlap may have areduced meaning when the time between successive heating events of asame spot is long enough to allow most of the heat to dissipate. Inaddition, the beam shape (generally non-uniform energy distribution)affects the actual amount of overlap. Thus, overlap regions 1204, 1208and 1210 may not experience significant synergistic effects. Optionally,however, the scan settings are selected to avoid too high energydeposition in any part of the sclera. In some cases, a portion of thesclera is not directly irradiated by laser but is close enough to one ortwo or more laser irradiations to become ablated.

Following is a short estimation of energy levels. For a spot size of 400micron diameter, power level of 24 watts, dwell time of 300 microsecondsand overlap of 30%, the energy applied at a shot is ˜7.5*10-3 Joule. Theenergy density is about 6 Joule/sqr.cm. This amount is consideredsufficient for ablation. This number is increased (e.g., but up to30%-50% for some portions) if one considers the overlap and somewhatreduced if losses in the system are considered. It is noted that forsome parts of the sclera the energy density is not uniform but may varywithin a factor of, for example, 1.2, 1.5, 2 or other factors.

In an exemplary embodiment of the invention, at least some of theoverlaps, for example, at least 30% or 50% of overlaps are overlappingin space but are not near in time, for example, allowing, between 1 and300 milliseconds, for example, between 10 and 100 milliseconds between afirst targeting and an overlapping targeting.

General

It should be noted that the above systems and methods may be used forparts of the sclera not only over the Schlemm's canal. It should benoted that some features, such as discovery of the SC, can be appliedusing non-laser techniques, such as a scalpel (although lasers may besafer and/or easier to use).

The above embodiments may be packaged in various manners, including, forexample, modules, add-ons for an OM and as part of an OM. Optionally,software for controlling the LACS is provided with a component of theLACS, for example, the scanner. Optionally, the aiming beam of the CO2laser is used to show the scan pattern exercised by the scanner.

It is expected that during the life of a patent maturing from thisapplication many relevant lasers and scanners will be developed and thescope of the terms “laser” and “scanner” are intended to include allsuch new technologies a priori.

As used herein the term “about” refers to ±10%.

The terms “comprises”, “comprising”, “includes”, “including”, “having”and their conjugates mean “including but not limited to”. This termencompasses the terms “consisting of” and “consisting essentially of”.

The phrase “consisting essentially of” means that the composition ormethod may include additional ingredients and/or steps, but only if theadditional ingredients and/or steps do not materially alter the basicand novel characteristics of the claimed composition or method.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise. For example,the term “a compound” or “at least one compound” may include a pluralityof compounds, including mixtures thereof.

The word “exemplary” is used herein to mean “serving as an example,instance or illustration”. Any embodiment described as “exemplary” isnot necessarily to be construed as preferred or advantageous over otherembodiments and/or to exclude the incorporation of features from otherembodiments.

The word “optionally” is used herein to mean “is provided in someembodiments and not provided in other embodiments”. Any particularembodiment of the invention may include a plurality of “optional”features unless such features conflict.

Throughout this application, various embodiments of this invention maybe presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Accordingly, the description of a range should be consideredto have specifically disclosed all the possible subranges as well asindividual numerical values within that range. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numberswithin that range, for example, 1, 2, 3, 4, 5, and 6. This appliesregardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to includeany cited numeral (fractional or integral) within the indicated range.The phrases “ranging/ranges between” a first indicate number and asecond indicate number and “ranging/ranges from” a first indicate number“to” a second indicate number are used herein interchangeably and aremeant to include the first and second indicated numbers and all thefractional and integral numerals therebetween.

As used herein the term “method” refers to manners, means, techniquesand procedures for accomplishing a given task including, but not limitedto, those manners, means, techniques and procedures either known to, orreadily developed from known manners, means, techniques and proceduresby practitioners of the chemical, pharmacological, biological,biochemical and medical arts.

As used herein, the term “treating” includes abrogating, substantiallyinhibiting, slowing or reversing the progression of a condition,substantially ameliorating clinical or aesthetical symptoms of acondition or substantially preventing the appearance of clinical oraesthetical symptoms of a condition.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

EXAMPLES

Various embodiments and aspects of the present invention as delineatedhereinabove and as claimed in the claims section below find experimentalsupport in the following example.

Evaluation of the Safety and Effectiveness of the OT-134 System in C0₂Laser Assisted Non-Penetrating Deep Sclerectomy. (Human Clinical Trials)

Methods:

A prospective single-arm, non-randomized, multi-center study. The studywas performed in accordance with the Declaration of Helsinki. All thesubjects or their legal guardians agreed to sign a written informedconsent prior to study participation.

The inclusion criteria were defined as follows: all subjects must be ≥18years of age, with clinical documented diagnosis of Primary Open AngleGlaucoma (POAG) or Pseudo-Exfoliative Glaucoma (PEXFG) in both eyes.Diagnosis-requires: glaucomatous optic neuropathy, Shaffer angle greaterthan grade 2 and visual field defect attributed to glaucoma. Allsubjects had an indication for primary filtration surgery due to thepresence of ocular hypertension, defined as an intraocular pressure(TOP)≥21 mm Hg in the study eye, as measured in 3 consecutive visitsover a 90 day period before enrollment, while on maximal toleratedhypotensive medications. The patients had to be phakic or pseudophakicin the operated eye with no associated ocular disorder or associatedocular diseases but cataract and no prior surgical or laser interventionin study eye but cataract surgery with clear corneal incision. The Bestcorrected visual acuity (BCVA) in the fellow eye had to be >20/200.

Exclusion Criteria:

Subjects with diagnosis of glaucoma other than POAG or PEXFG, or dilatedpupil diameter of less than 2 mm were excluded from the study as well assubjects with known allergy to the study medications or severe systemicdisease and disabling conditions.

The baseline evaluation of all subjects was conducted prior to thesurgical procedure and included the following: demographic details,general medical history, and ophthalmic history. Glaucoma history wasdocumented, including: family history, disease duration, anti-glaucomatreatments in the past (medications & interventions), IOP control anddisease progression analysis according to visual fields and optic discsdamage.

All subjects were examined and the pre-operative ocular status wasdocumented, including: refraction and best corrected visual acuity(BCVA) as measured with ETDRS chart. Biomicroscopic examination waspreformed and the average of 3 repeated IOP measurements, using aGoldman tonometer, was recorded. Further baseline evolution alsoincluded: a gonioscopic examination, an average of 3 repeatedmeasurements of central corneal thickness. Fundus examination and opticdisc evaluation were performed, with attention to: C/D ratio, discnotches, splinters hemorrhages and discs size. A threshold 24-2 Humphreyperimetry, within 2 weeks prior to surgery, and stereoscopic discphotography were recorded.

Safety outcomes were defined as follows;

Overall incidence of intra-operative device related adverse events

Early post-operative device related adverse events (through Day 7);

Cumulative and persistent (present at 3 and 6 months) device relatedadverse events.

Performance Endpoints:

1. Qualified Success Rate at 3 months (Rate of patients with IOP<21 mmHgwith or without glaucoma medications at 3 months).

2. Complete Success Rate at 3 months (Rate of patients with IOP<21 mmHgwithout glaucoma medications at 3 months).

3. Failure rate: The definition of failure in the study: IOP<5, IOP>21mmHg, complete loss of vision or performance of additional glaucomasurgery except for goniopuncture and needling.

4. Incidence of intra-operative perforations (macro).

The Surgical Procedure:

The surgery was preformed under local anesthesia.

Following routine preparation of the eye for sterile surgicalconditions, a fornix-based peritomy was performed at the superiorlimbus, and the Tenon's capsule was dissected to expose the sclera. Apartial thickness (one-third to one-half) limbal-based scleral flap upto 5×5 mm was be dissected at the limbus into clear cornea. The scanningshape and area size were set and the laser beam was focused. The treatedarea on the patient was defined and verified with the red aiming diodelaser. The laser power, mode, laser beam focus, scanner dwell time,overlap, and repeat delay were verified. The cornea was protected with awet sponge. The laser beam was applied to the scleral wall in an areathat included the Schlemm's Canal until the outer wall of the Schlemm'sCanal was ablated. The charred tissue was wiped after ablation every 1-3laser scans, scanning proceeded until percolation was achieved andpercolation zone length measured at least 2.5 mm. Prior to flap suture,Healon 5 was applied beneath the repositioned flap and the scleral flapwas repositioned and secured in place using 2 interrupted 10-0 nylonsutures. The conjunctiva was repositioned and secured in place usinginterrupted 10-0 nylon sutures. Careful hemostasis was performed duringthe entire procedure. Antibiotic and steroid ointment were applied andthe eye will be closed with a patch and shield.

Follow Up:

All subjects were examined according to the following schedule: 24(±12)hours post-operatively, at week 1 and 3 (±3 days), at week 6 and 14 (±2weeks), and 6 months (±2 weeks) after surgery.

Statistical Methods:

The following statistical tests were used in the analysis of the datapresented in this study:

Descriptive statistics: continuous variables were summarized using themean, median, standard error, minimum and maximum values. Categoricalvariables were summarized using frequency counts and percentages.

95% Confidence Interval was calculated for the mean IOP measurements.

95% Confidence Interval was calculated for the Rate of success asdefined in the primary and secondary endpoints.

Paired T-test was applied for testing the statistical significance ofthe changes in IOP. All tests applied were two-tailed, and p value of 5%or less was considered statistically significant. The data was analyzedusing the SAS® software (SAS Institute, Cary N.C.).

Results;

Thirty seven subjects were included in the study. The study includes atotal of 37 subjects from 3 sites: Mexico (14 subjects), India (13subjects) and Russia (10 subjects). Mean age 64.1. 24.3% had PEXFG whilethe remaining 75.7% had POAG. Mitomycin C was used in 26.5% of thepatients.

One subject was lost to follow up 6 weeks post surgery. 1 subject passedaway due to Diabetes Mellitus complications 4 weeks post surgery. 1subject was retrospectively excluded from the analysis of the results ashe underwent YAG laser iridotomy pre-operatively.

3 patients were converted into standard trabeculectomy during theinitial procedure due to protocol deviation as the initial scanning arefailed to reach the area of Schlemm's canal. One subject underwent tubeshunt surgery 4 weeks after the initial procedure as his IOP wasuncontrolled. This patient was related as a failure and his intra-ocularpressures and hypotensive medications were analyzed up to tubeimplantation point.

The results of the remaining 30 patients were analyzed as follows:

Schlemm's canal was easily recognized and treated in all 30 subjects.

Adequate percolation was achieved in all cases.

The average pre-op IOP was 26.16 mmHg (median 24.00 mmHg) as compared toan average IOP of 14 mmHg (median 14.00 mmHg) at 6 months (p<0.001). Theaverage IOP reduction was 44.05%.(FIG. 13)

The complete success rate was 86.7% at 6 months (IOP<18 mmHg withouthypotensive medications). (FIG. 16)

The qualified success rate was 93.3% at 6 months (IOP<18 mmHg with andwithout hypotensive medications). (FIG. 16)

3 subjects were considered as failure: 1 underwent tube shunt procedure4 weeks after the initial procedure due to uncontrolled IOP and theother two subjects had IOP>21 mmHg

The average number of pre-operative hypotensive medications per patientwas 2.3 as compared to 0.27 hypotensive medications per patient at 6months (p<0.001).—(FIG. 14)

FIG. 15 shows the IOP results in the different sites. The similarity ofthe three graphs demonstrates the reproducibility of the results.

Post Operative Procedures:

Seven needling procedures were preformed in 6 subjects. One needlingprocedure was preformed 1 week after surgery, two were preformed 2 weekspost-surgery and 4 were preformed 6 weeks post initial procedure

Two goniopuncture procedures were performed (2 and 4 weeks after theinitial procedure).

One laser suture lysis was preformed 1 week post initial surgery.

No serious adverse events were recorded. No intra-operative devicerelated adverse events were recorded. There were no intra-operativedevice technical issues operating the CO2 laser system. There were nocases of vision loss or of infection.

Documented adverse events: Mild-moderate peripheral anterior synechia(PAS) was recorded in 3 subjects and required no treatment.

Mild-moderate early post operative wound leak was inspected in 2 cases.Both resolved with conservative treatment (bandage contact lens).

One case of mild hyphema was recorded in one subject and wasspontaneously absorbed.

Three cases of mild corneal complications were documented (1 milddellen, and 2 superficial erosions). All three resolved withconservative treatment.

CONCLUSIONS

The above experiments support the conclusion that CO2 laser assisted nonpenetrating deep sclerectomy is a highly effective, safe and relativelysimple surgical procedure for lowering and control of the IOP inglaucoma and other patients. Laboratory studies and clinical experienceexhibit a high safety profile and very promising mid-term clinicalresults.

The good results at 6 months follow up, the safety profile and thesimple procedure are very relevant to all glaucoma patients and shouldbe considered as an option of a first line procedure for patients withelevated IOP.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention. To the extent thatsection headings are used, they should not be construed as necessarilylimiting.

1-91. (canceled)
 92. A laser ablation control system, comprising: (a) acard reader; (b) a laser beam controller; (c) circuitry configured tocontrol one or both of said laser beam controller and a laser beamsource in accordance with data read by said card reader to performablation.
 93. The system according to claim 92, wherein said circuitryprevents a firing of an ablation laser by said laser beam controller.94. The system according to claim 92, wherein said circuitry prevents ascanning of an ablation laser by said laser beam controller.
 95. Thesystem according to claim 92, wherein said circuitry limits a time ofactivation of said controller.
 96. The system according to claim 95,wherein said circuitry allows reuse of a card and debts a later readcard.